Synthesis Of Cell-Penetrating Peptides Research Articles

DeepCPPred: A Deep Learning Framework for the Discrimination of Cell-Penetrating Peptides and Their Uptake Efficiencies.

Cell-penetrating peptides (CPPs) are special peptides capable of carrying a variety of bioactive molecules, such as genetic materials, short interfering RNAs and nanoparticles, into cells. Recently, research on CPP has gained substantial interest from researchers, and the biological mechanisms of CPPS have been assessed in the context of safe drug delivery agents and therapeutic applications. Correct identification and synthesis of CPPs using traditional biochemical methods is an extremely slow, expensive and laborious task particularly due to the large volume of unannotated peptide sequences accumulating in the World Bank repository. Hence, a powerful bioinformatics predictor that rapidly identifies CPPs with a high recognition rate is urgently needed. To date, numerous computational methods have been developed for CPP prediction. However, the available machine-learning (ML) tools are unable to distinguish both the CPPs and their uptake efficiencies. This study aimed to develop a two-layer deep learning framework named DeepCPPred to identify both CPPs in the first phase and peptide uptake efficiency in the second phase. The DeepCPPred predictor first uses four types of descriptors that cover evolutionary, energy estimation, reduced sequence and amino-acid contact information. Then, the extracted features are optimized through the elastic net algorithm and fed into a cascade deep forest algorithm to build the final CPP model. The proposed method achieved 99.45 percent overall accuracy with the CPP924 benchmark dataset in the first layer and 95.43 percent accuracy in the second layer with the CPPSite3 dataset using a 5-fold cross-validation test. Thus, our proposed bioinformatics tool surpassed all the existing state-of-the-art sequence-based CPP approaches.

Bioconjugates of Co(III) complexes with Schiff base ligands and cell penetrating peptides: Solid phase synthesis, characterization and antiproliferative activity

In this work we synthesized a chelating Schiff base by a single condensation of salicylaldehyde with 3,4-diamino benzoic acid (1). This ligand was used further for complexation to CoCl2·6H2O under nitrogen. In the next step, three six-coordinate Co(III) complexes were synthesized by coordinating this complex with imidazole (2), 2-methyimidazole (3) and N-Boc-l-histidine methyl ester (4) (Boc: tert.-butoxycarbonyl) in axial positions with simultaneous oxidation of Co(II) to Co(III) under ambient environment. All Co(III) complexes were characterized by multinuclear NMR spectroscopy (1H, 13C and 59Co NMR), FT-IR, mass spectrometry and HPLC. The Co(III) complexes were conjugated to three different cell penetrating peptides: FFFF (P1), RRRRRRRRRGAL (P2) and FFFFRRRRRRRRRGAL (P3). Standard solid-phase peptide chemistry was used for the synthesis of cell penetrating peptides. Coupling of N-terminal peptides with the cobalt complexes, possessing a carboxylic group on the tetradentate Schiff base ligand, afforded Co(III)-peptide bioconjugates, which were purified by semi-preparative HPLC and characterized by analytical HPLC and mass spectrometry. The antiproliferative activity of the synthesized compounds was studied against different human tumour cell lines: lung cancer A549, liver cancer HepG2 and normal human fibroblasts GM5657T, in comparison with the activity of cisplatin as a reference drug. The bioconjugate 21 containing the Co complex 4 and the combined phenylalanine and polyarginine cell penetrating sequence P3 shows better activity against the liver cancer line HepG2 than the parent Co(III) complex 4.

Design and Synthesis of Cell‐Penetrating Peptides

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