Microwave-assisted Solid-phase Synthesis Research Articles

Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups

Unnatural amino acids, amino acids containing side-chain functionalities not commonly seen in nature, are increasingly found in synthetic peptide sequences. Synthesis of some unnatural amino acids often includes the use of a precursor consisting of a Schiff-base stabilized by a nickel cation. Unnatural side-chains can be installed on an amino acid backbone found in this Schiff-base complex. The resulting unnatural amino acid can then be isolated from this complex using hydrolysis of the Schiff-base, typically by employing reflux in strongly acidic solution. These highly acidic conditions may remove acid-labile side-chain protecting groups necessary for the unnatural amino acids to be used in microwave-assisted solid-phase peptide synthesis. In this work, we present an efficient hydrolysis and subsequent Fmoc protection of an amino acid isolated from a Ni-Schiff base complex. Hydrolysis conditions presented in this work are suitable for retention of acid-labile side-chain protecting groups and may be adaptable to a variety of unnatural amino acid substrates.

Hydrolysis of a Ni-Schiff-Base Complex Using Conditions Suitable for Retention of Acid-labile Protecting Groups.

Unnatural amino acids, amino acids containing side-chain functionalities not commonly seen in nature, are increasingly found in synthetic peptide sequences. Synthesis of some unnatural amino acids often includes the use of a precursor consisting of a Schiff-base stabilized by a nickel cation. Unnatural side-chains can be installed on an amino acid backbone found in this Schiff-base complex. The resulting unnatural amino acid can then be isolated from this complex using hydrolysis of the Schiff-base, typically by employing reflux in strongly acidic solution. These highly acidic conditions may remove acid-labile side-chain protecting groups necessary for the unnatural amino acids to be used in microwave-assisted solid-phase peptide synthesis. In this work, we present an efficient hydrolysis and subsequent Fmoc protection of an amino acid isolated from a Ni-Schiff base complex. Hydrolysis conditions presented in this work are suitable for retention of acid-labile side-chain protecting groups and may be adaptable to a variety of unnatural amino acid substrates.

Short communication: Measuring the angiotensin-converting enzyme inhibitory activity of an 8-amino acid (8mer) fragment of the C12 antihypertensive peptide

An 8-AA (8mer) fragment (PFPEVFGK) of a known antihypertensive peptide derived from bovine αS1-casein (C12 antihypertensive peptide) was synthesized by microwave-assisted solid-phase peptide synthesis and purified by reverse phase HPLC. Its ability to inhibit angiotensin-converting enzyme (ACE) was assessed and compared with that of the parent 12mer peptide (FFVAPFPEVFGK) to determine the effect of truncating the sequence on overall hypotensive activity. The activity of the truncated 8mer peptide was found to be almost 1.5 times less active than that of the 12mer, with ACE-inhibiting IC50 (half-maximal inhibitory concentration) values of 108 and 69μM, for the 8mer and 12mer, respectively. Although the 8mer peptide is less active than the original 12mer peptide, its overall activity is comparable to activities reported for other small proteins that elicit physiological responses within humans. These results suggest that microbial degradation of the 12mer peptide would not result in a complete loss of antihypertensive activity if used to supplement fermented foods and that the stable 8mer peptide could have potential as a blood pressure–lowering agent for use in functional foods.

Solid-phase synthesis of C-mannosylated glycopeptide on WSXWS motif of human erythropoietin receptor

Protein C-mannosylation is a widely conserved posttranslational modification in multicellular organisms although the function of this modification is yet to be clarified. To evaluate the effect of this modification, a C-mannosyltryptophan containing glycopeptide of human erythropoietin receptor (EPOR), which includes WSXWS motif conserved in cytokine receptor superfamily, was synthesized by microwave assisted solid-phase synthesis using per-O-benzyl protected amino acids and C-mannosyltryptophan on Sieber amide resin. Comparative NMR analysis of the C-mannosyl glycopeptide and a corresponding naked peptide revealed that the C-mannosylation enhances the NOE signal between the peptide main chain and the aromatic side chain to suggest enhancement of conformational stability of the WSXWS motif and its surrounding regions.

Solid phase synthesis of oligoethylene glycol-functionalized quinolinecarboxamide foldamers with enhanced solubility properties

Abstract A series of octameric quinoline oligoamide foldamers has been synthesized consisting exclusively of monomers which display mono-, di-, tri- or tetra-ethylene glycol side-chains. These oligomers adopt stable helical conformations. New Fmoc-acid monomer precursors were first developed. The microwave assisted solid-phase synthesis (SPS) methodology for oligomer preparation is described, and it is demonstrated that small adjustments in side-chain length translate into large differences in the solubility profile of the oligomers. The impact of such modifications on foldamer preparation, handedness inversion kinetics and potential applications is also discussed.

The Use of Microwave-Assisted Solid-Phase Peptide Synthesis and Click Chemistry for the Synthesis of Vaccine Candidates Against Hookworm Infection.

A protein-based vaccine approach against hookworm infection has failed to deliver the expected outcome, due to a problem with an allergic response in the patient or difficulties in the proteins' production. This implication could be overcome by using a chemically synthesized peptide-based vaccine approach. This approach utilizes minimal pathogenic components that are necessary for the stimulation of the immune response without triggering adverse side effects. To boost the peptide's immunogenicity, a lipid core peptide (LCP) system can be utilized as a carrier molecule/immunostimulant. This chapter describes in detail the synthesizing of protected lipoamino acid, the self-adjuvanting moiety (LCP core), the peptide epitope, and the final vaccine candidate. The subunit peptide and the LCP core were synthesized using microwave-assisted solid-phase peptide synthesis (SPPS). Then the final hookworm vaccine construct was assembled using the copper-catalyzed azide-alkyne cycloaddition, or "click," reaction.

Facile Microwave-Assisted Solid-Phase Synthesis of Highly Fluorescent Nitrogen-Sulfur-Codoped Carbon Quantum Dots for Cellular Imaging Applications.

Carbon quantum dots (CQDs) have recently attracted significant attention for both their fundamental science and technological applications as a new class of fluorescent zero-dimensional nanomaterials with a size below 10 nm. However, the reported methods of synthesis were generally less suitable for the large-scale production of the CQDs with high-fluorescent quantum yield (QY). In the paper, a novel one-pot microwave-assisted drying synthesis approach was presented to prepare CQDs with high QY of 61.3 % for the first time. The production yield of CQDs was 35±3 % in weight. The as-prepared CQDs were characterized by various techniques such as TEM, AFM, XRD, XPS, FTIR spectroscopy, UV/Vis absorption spectroscopy, and fluorescence spectroscopy. The results showed that the high QY of CQDs was largely attributed to the dual doping of nitrogen and sulphur into CQDs. Such CQDs were then used as live-cell imaging reagents due to their high QY, good water dispersibility, fine biocompatibility, high photostability, and low cytotoxicity.

Microwave-assisted solid-phase peptide synthesis of neurosecretory protein GL composed of 80 amino acid residues.

We recently identified a novel cDNA encoding a small secretory protein of 80 amino acid residues, termed neurosecretory protein GL (NPGL), from the chicken hypothalamus. Homologs of NPGL have been reported to be present in mammals, such as human and rat. NPGL is amidated at its C-terminus, contains an intramolecular disulfide bond, and is hydrophobic in nature. In this study, we have optimized the synthesis of the entire 80-amino acid peptide sequence of rat NPGL by microwave-assisted solid-phase peptide synthesis. NPGL was obtained with a 10% yield when the coupling reactions were performed using 1-[Bis(dimethylamino)methylene]-1H-1,2,3-triazolo[4,5-b]pyridinium-3-oxid hexafluorophosphate (HATU) at 50 °C for 5 min, and Fmoc deprotections were performed using 40% piperidine containing 0.1 M HOBt. Furthermore, the disulfide bond of NPGL was formed with 20% yield with the use of glutathione-containing redox buffer and 50% acetonitrile.

Click To Bind: Microwave-Assisted Solid-Phase Synthesis of Peptoids Incorporating Pyridine–Triazole Ligands and Their Copper(II) Complexes

We describe a fast and efficient incorporation of the ligands 2-(1<i>H</i>-1,2,3-triazol-4-yl)pyridine and 2-(1<i>H</i>-1,2,3-triazol-1-ylmethyl)-pyridine into N-substituted glycine peptoid oligomers by the azide–alkyne cycloaddition (click) reaction on a solid support under microwave irradiation. Peptoids bearing these ligands formed stable complexes with copper(II).

Abstract 3238: The transmembrane domain of prostate-specific membrane antigen: Its role in oligomerization and activation in prostate cancer and nonprostatic neovasculature

Abstract Prostate cancer (PCa) is the second leading cause of cancer-related deaths among American men. The high expression of the membrane protein called prostate specific membrane antigen (PSMA) is implicated in PCa invasiveness as well as neovasculature of nonprostatic solid tumors. Little is known about the exact role of PSMA in PCa progression albeit it is one of the most validated biomarker for the diagnosis and detection of PCa. The functional form of PSMA occurs as a non-covalent homodimer, which is a common motif among bitopic membrane proteins. Further, it is widely recognized that many membrane proteins participate in intracellular signal transduction through the lateral association of their transmembrane domains (TMDs), but this has not been directly demonstrated in PSMA. We hypothesize that PSMA TMD participates in oligomerization and subsequent activation of PSMA. Thus, to gain insight into the non-covalent assembly of PSMA, we aim to determine if the isolated PSMA TMD peptide forms a dimer and if the treatment of full-length PSMA with exogenous PSMA TMD peptide will perturb its properties. Studies using isolated TMDs have been widely used to probe protein-protein interactions and provide useful information on protein assembly under membrane mimetic systems. We identified the amino acid sequence and designed the isolated PSMA TMD peptide based on a known human PSMA sequence (UniProt accession code: Q04609). Two Lysine residues ware appended at both the N- and C-termini to increase the solubility of this highly hydrophobic peptide in polar solvents. Our initial studies revealed that the TMD has twenty-four residues and contains two repeat units of the Small-XXX-Small motif. This sequence is known to be crucial in inducing a strong self-assembly as observed in the bitopic protein Glycophorin A. We prepared the PSMA TMD peptide by microwave-assisted solid phase synthesis and purified by high performance liquid chromatography. The peptide was analyzed by MALDI-TOF mass spectrometry to establish homogeneity and by circular dichroism to examine its secondary structure in membrane mimetic environment. We investigated the oligomerization of the peptide using SDS-PAGE gel shift and fluorescence self-quenching assays. We tested the effect of the peptide against PSMA using an established assay. Herein we report on the oligomerization and PSMA binding properties of PSMA TMD. Our findings may shed light on the role of PSMA TMD in PSMA oligomerization and its potential as a model peptide that target transmembrane helices. It may also aid in the rational design and development of peptide probes for protein-protein interactions as well as therapeutics that target cancer- and clinically-relevant membrane proteins. Citation Format: Brianna S. Berg, Brandan M. Cook, Nathan Beattie, Cliff E. Berkman, Jonel P. Saludes. The transmembrane domain of prostate-specific membrane antigen: Its role in oligomerization and activation in prostate cancer and nonprostatic neovasculature. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3238. doi:10.1158/1538-7445.AM2014-3238

Rapid and convenient semi-automated microwave-assisted solid-phase synthesis of arylopeptoids

A facile and expedient route to the synthesis of arylopeptoid oligomers (N-alkylated aminomethyl benz-amides) using semi-automated microwave-assisted solid-phase synthesis is presented. The synthesis was optimized for the incorporation of side chains derived from sterically hindered or unreactive amines and both ortho- and para-substituted arylo-backbones. By utilizing this optimized protocol a complex nonameric arylopeptoid was synthesized in less than 11h, featuring a novel alternating ortho-, meta-, and para-substituted backbone pattern and a variety of chemically diverse and challenging side chains.

Aqueous microwave-assisted solid-phase peptide synthesis using Fmoc strategy. III: Racemization studies and water-based synthesis of histidine-containing peptides

In this study, we describe the first aqueous microwave-assisted synthesis of histidine-containing peptides in high purity and with low racemization. We have previously shown the effectiveness of our synthesis methodology for peptides including difficult sequences using water-dispersible 9-fluorenylmethoxycarbonyl-amino acid nanoparticles. It is an organic solvent-free, environmentally friendly method for chemical peptide synthesis. Here, we studied the racemization of histidine during an aqueous-based coupling reaction with microwave irradiation. Under our microwave-assisted protocol using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride, the coupling reaction can be efficiently performed with low levels of racemization of histidine. Application of this water-based microwave-assisted protocol with water-dispersible 9-fluorenylmethoxycarbonyl-amino acid nanoparticles led to the successful synthesis of the histidine-containing hexapeptide neuropeptide W-30 (10-15), Tyr-His-Thr-Val-Gly-Arg-NH₂, in high yield and with greatly reduced histidine racemization.

Effect of Grafted Oligopeptides on Friction

Frictional and normal forces in aqueous solution at 25 °C were measured between a glass particle and oligopeptide films grafted from a glass plate. Homopeptide molecules consisting of 11 monomers of either glutamine, leucine, glutamic acid, lysine, or phenylalanine and one heteropolymer were each "grafted from" an oxidized silicon wafer using microwave-assisted solid-phase peptide synthesis. The peptide films were characterized using X-ray photoelectron spectroscopy and secondary ion mass spectrometry. Frictional force measurements showed that the oligopeptides increased the magnitude of friction compared to that on a bare hydrophilic silicon wafer but that the friction was a strong function of the nature of the monomer unit. Overall we find that the friction is lower for more hydrophilic films. For example, the most hydrophobic monomer, leucine, exhibited the highest friction whereas the hydrophilic monomer, polyglutamic acid, exhibited the lowest friction at zero load. When the two surfaces had opposite charges, there was a strong attraction, adhesion, and high friction between the surfaces. Friction for all polymers was lower in phosphate-buffered saline than in pure water, which was attributed to lubrication via hydrated salt ions.

Microwave-Assisted Solid-Phase Synthesis of a 1,2-Disubstituted Benzimidazole Library by Using a Phosphonium Linker

An efficient and rapid microwave-assisted solid-phase method for the synthesis of 5-methyl-1,2-disubstituted benzimidazoles derivatives has been developed. The phosphonium linker, obtained by reaction between polymer-supported triphenylphosphine and 4-fluoro-3-nitrobenzyl iodide, underwent aromatic substitution with primary amines, followed by one-pot reaction with aldehydes in the presence of SnCl2·2H2O, yielded the benzimidazole system under microwave irradiation. The final products were released from the resin with NaOH under microwave irradiation and were obtained in high purity and good overall yield.

A novel approach for the parallel synthesis of glycopeptides by combining solid-phase peptide synthesis and dendrimer-supported enzymatic modifications

Functionalized, high-generation (G7) polyamidoamine (PAMAM) dendrimers are a convenient scaffold for the fully automated enzymatic synthesis of oligosaccharides such as biologically important sialyl Lewis X tetrasaccharide derivatives. In this study, we expanded this strategy to the synthesis of more complicated glycopeptides by assessing the feasibility of G7 PAMAM dendrimer-based polymer supports for attaching glycopeptide intermediates during the subsequent enzymatic modification steps. A monosaccharide-attached glycopeptide containing an N-terminal heterobifunctional linker was prepared by microwave-assisted solid-phase synthesis and was coupled with an aminooxy-functionalized G7 PAMAM dendrimer through oxime bond formation. This reaction proceeded smoothly at pH 4 and afforded the conjugates in 98% yield when 0.2 equivalents of the glycopeptide were combined with 1 equivalent of the aminooxy group of dendrimer. Although modifications using recombinant human β1,4-galactosyltransferase/uridine-5′-diphospho-α-D-galactose disodium salt and recombinant rat α2,3-sialyltransferase/cytidine-5′-monophospho-β-D-N-acetylneuraminic acid disodium salt gave the trisaccharide Neu5Acα2,3Galβ1,4GlcNAc in quantitative yields, treatment with recombinant human α1,3-fucosyltransferase in the presence of excess guanosine 5′-diphospho-β-L-fucose disodium salt did not convert this trisaccharide into the tetrasaccharide sialyl Lewis X tetrasaccharide on the dendrimer. Further optimization studies are required to improve the efficiency of branched-type sugar elongations and product release from polymers by selective peptidases for constructing a high-throughput glycopeptide synthetic system. Toward parallel enzymatic synthesis of biologically and pharmaceutically important glycopeptides, we investigated the feasibility of aminooxy-functionalized G7 PAMAM dendrimer derivative in the enzyme-assisted synthesis of glycopeptides having oligosaccharide side chains. The G7 PAMAM dendrimer was proved to become a nice supporting material that exhibited 99% recovery in a simple centrifugal ultrafiltration (UF) procedure in comparison with the hollow-fiber UF module (86%) used in the high-performance liquid chromatography-based automated glycan synthesizer. An optimization of the protocol was performed for the synthesis of glycopeptides bearing di-, tri- and tetrasaccharide branches.

Microwave‐Assisted Solid‐Phase Synthesis of Antifreeze Glycopeptides

Microwave-assisted solid-phase synthesis allows for the rapid and large-scale preparation and structure-activity characterization of tandem repeating glycopeptides, namely monodispersed synthetic antifreeze glycopeptides (syAFGPs, H-[Ala-Thr(Galβ1,3GalNAcα1→)-Ala]n -OH, n=2-6). By employing novel AFGP analogues, we have demonstrated that of the monodispersed syAFGPn (n=2-6, degree of polymerization, DP=2-6, Mw =1257-3690 Da), syAFGP5 (DP=5, Mw =3082 Da) and syAFGP6 (DP=6, Mw =3690 Da) exhibit the ability to form typical hexagonal bipyramidal ice crystals and satisfactory thermal hysteresis activity. Structural characterization by NMR and CD spectroscopy revealed that syAFGP6 forms a typical poly-L-proline type II helix-like structure in aqueous solution whereas enzymatic modification by sialic acid of the residues at the C-3 positions of the nonreducing Gal residues disturbs this conformation and eliminates the antifreeze activity.

Photodynamic Control of Bioactivity in a Nanofiber Matrix

Self-assembling peptide materials have been used extensively to mimic natural extracellular matrices (ECMs) by presenting bioactive epitopes on a synthetic matrix. Although this approach can facilitate a desired response from cells grown in the matrix, it lacks the capacity for spatial or temporal regulation of the presented signals. We describe here a photoresponsive, synthetic ECM using a supramolecular platform composed of peptide amphiphiles (PAs) that self-assemble into cylindrical nanofibers. A photocleavable nitrobenzyl ester group was included in the peptide backbone using a novel Fmoc-amino acid that is compatible with microwave-assisted solid-phase peptide synthesis. The placement of the photolabile group on the peptide backbone enabled efficient removal of the ECM-derived cell adhesion epitope RGDS from PA molecules upon exposure to light (half-life of photolysis ~1.9 min) without affecting the nanofiber assembly. Fibroblasts cultured on RGDS-presenting PA nanofiber substrates demonstrated increased cell spreading and more mature focal adhesions compared with unfunctionalized and control (RGES-presenting) surfaces, as determined by immunostaining and cell morphological analysis. Furthermore, we observed an arrest in fibroblast spreading on substrates containing a cleavable RGDS epitope when the culture was exposed to light; in contrast, this dynamic shift in cell response was absent when the RGDS epitope was attached to the PA molecule by a light-insensitive control linker. Light-responsive bioactive materials can contribute to the development of synthetic systems that more closely mimic the dynamic nature of native ECM.

Synthesis of Cyclic Py-Im Polyamide Libraries

Cyclic Py-Im polyamides containing two GABA turn units exhibit enhanced DNA binding affinity, but extensive studies of their biological properties have been hindered due to synthetic inaccessibility. A facile modular approach toward cyclic polyamides has been developed via microwave-assisted solid-phase synthesis of hairpin amino acid oligomer intermediates followed by macrocyclization. A focused library of cyclic polyamides 1–7 targeted to the androgen response element (ARE) and the estrogen response element (ERE) were synthesized in 12–17% overall yield. The Fmoc protection strategy also allows for selective modifications on the GABA turn units that have been shown to improve cellular uptake properties. The DNA binding affinities of a library of cyclic polyamides were measured by DNA thermal denaturation assays and compared to the corresponding hairpin polyamides. Fluorescein-labeled cyclic polyamides have been synthesized and imaged via confocal microscopy in A549 and T47D cell lines. The IC50 values of compounds 1–7 and 9–11 were determined, revealing remarkably varying levels of cytotoxicity.

ChemInform Abstract: Recent Advances in Microwave‐Assisted Solid‐Phase Synthesis of Heterocycles.

ChemInformVolume 43, Issue 26 Reviews ChemInform Abstract: Recent Advances in Microwave-Assisted Solid-Phase Synthesis of Heterocycles. Prasad Appukkuttan, Prasad Appukkuttan Lab. Org. Microwave-Assisted Chem., Dep. Chem., Univ. Leuven, B-3001 Leuven, Belg.Search for more papers by this authorVaibhav Vaibhav, Vaibhav Vaibhav Lab. Org. Microwave-Assisted Chem., Dep. Chem., Univ. Leuven, B-3001 Leuven, Belg.Search for more papers by this authorP. Mehta, P. Mehta Lab. Org. Microwave-Assisted Chem., Dep. Chem., Univ. Leuven, B-3001 Leuven, Belg.Search for more papers by this authorErik Van der Eycken, Erik Van der Eycken Lab. Org. Microwave-Assisted Chem., Dep. Chem., Univ. Leuven, B-3001 Leuven, Belg.Search for more papers by this author Prasad Appukkuttan, Prasad Appukkuttan Lab. Org. Microwave-Assisted Chem., Dep. Chem., Univ. Leuven, B-3001 Leuven, Belg.Search for more papers by this authorVaibhav Vaibhav, Vaibhav Vaibhav Lab. Org. Microwave-Assisted Chem., Dep. Chem., Univ. Leuven, B-3001 Leuven, Belg.Search for more papers by this authorP. Mehta, P. Mehta Lab. Org. Microwave-Assisted Chem., Dep. Chem., Univ. Leuven, B-3001 Leuven, Belg.Search for more papers by this authorErik Van der Eycken, Erik Van der Eycken Lab. Org. Microwave-Assisted Chem., Dep. Chem., Univ. Leuven, B-3001 Leuven, Belg.Search for more papers by this author First published: 31 May 2012 https://doi.org/10.1002/chin.201226243AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume43, Issue26June 26, 2012 RelatedInformation

Abstract 4745: Multivalent dendrimeric peptides as new biomarker probes for the detection of cancer metastasis

Abstract Malignant tumor cells overexpress and release lipid vesicles called exosomes into the body fluids to facilitate their movement and metastasis to other parts of the body. It was found that an increased secretion of exosomes in the peripheral blood is correlated with lung cancer and melanoma metastasis. The hallmarks of exosomes are their highly curved surface (d = ∼30-100 nm) that is distinct from other extracellular lipid vesicles and their enrichment with the anionic lipid phosphatidylserine (PS) in the outer leaflet of the membrane bilayer. These properties provide an opportunity in selectively targeting exosomes as potential cancer biomarkers. Current clinical methods that are being used to classify metastatic patients are not accurate or reproducible, are often problematic, and do not indicate whether or not treatment is reducing metastasis. Furthermore, these methods involve invasive procedures. We aim to develop a novel, minimally invasive, peptide-based diagnostic tool to detect and visualize exosomes and measure exosome oversecretion in cancer patients. The successful creation of this diagnostic tool for cancer metastasis will help in the proper diagnosis and therapy for cancer patients. We chose the small peptide Bradykinin (BK) as our core molecule because it was recently reported that this peptide differentially interacts with nanometer size synthetic lipid vesicles, with preferential binding for vesicles with higher anionic lipid composition. Our earlier studies on a BK analogue showed that it selectively binds to synthetic lipid vesicles with d = 55 +/− 5 nm, dimensions that mimic the size of exosomes. We hypothesized that by creating a library of multivalent, dendrimeric analogues of BK, we could increase its binding affinity to lipid vesicle models that would translate to the detection of exosomes in body fluids. The peptide was prepared by microwave-assisted solid phase synthesis, was modified with Lys-Gly spacers, the epsilon-amino of the Lys residue was deprotected and converted into an azide, and the peptide was labeled with a fluorophore, cleaved from the resin, and purified by high performance liquid chromatography. We also synthesized a series of dendrimer-type, alkyne functionalized, aromatic small molecules as scaffolds in the preparation of the multivalent dendrimeric peptides. The azide-functionalized BK analogue was conjugated to the scaffolds using solution phase Copper-catalyzed azide-alkyne cycloaddition reaction (‘Click’ chemistry). We investigated the curvature sensing ability of the peptides using synthetic liposomes and exosomes from the plasma of a rat model using a combination of spectroscopic techniques. The lipid vesicle detecting properties of these peptides and their potential as new diagnostic tool for cancer metastasis shall be reported herein. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4745. doi:1538-7445.AM2012-4745