Abstract
To obtain different amino acids with varying lipophilicity and that can carry up to three positive charges we have developed a number of new triamino acid building blocks. One set of building blocks was achieved by aminoethyl extension, via reductive amination, of the side chain of ortnithine, diaminopropanoic and diaminobutanoic acid. A second set of triamino acids with the aminoethyl extension having hydrocarbon side chains was synthesized from diaminobutanoic acid. The aldehydes needed for the extension by reductive amination were synthesized from the corresponding Fmoc-L-2-amino fatty acids in two steps. Reductive amination of these compounds with Boc-L-Dab-OH gave the C4-C8 alkyl-branched triamino acids. All triamino acids were subsequently Boc-protected at the formed secondary amine to make the monomers appropriate for the N-terminus position when performing Fmoc-based solid-phase peptide synthesis.
Highlights
Lipophilicity has immense importance for pharmacological properties
Arginine-based double-tailed lipid-peptide conjugates with a positive charge were synthesized as a potent nucleic acid transporter [4]
We found that reductive amination reaction between Nα-Fmoc-protected amino aldehydes and side chain primary amine of the Nα-Boc-protected diamino carboxylic acids would provide us the basic structural moiety of the target molecules
Summary
Lipophilicity has immense importance for pharmacological properties. Drug molecules are required to have lipophilic properties to accomplish a desired pharmacokinetic profile [1]. Protecting groups of these triamino acids have been manipulated in such a way that the final monomers would be suitable for their incorporation at the N-terminus end of a peptide/peptoid sequence by the Fmoc-strategy through solid-phase peptide synthesis, while still enabling further functionalization of the side chain. We found that reductive amination reaction between Nα-Fmoc-protected amino aldehydes and side chain primary amine of the Nα-Boc-protected diamino carboxylic acids would provide us the basic structural moiety of the target molecules.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
