Synthesis of hybrid hydrazino peptides: protected vs unprotected chiral α-hydrazino acids.

Josipa Suć,Ivanka Jerić

doi:10.1186/s40064-015-1288-9

Abstract

Peptidomimetics based on hydrazino derivatives of α-amino acids represent an important class of peptidic foldamers with promising biological activities, like protease inhibition and antimicrobial activity. However, the lack of straightforward method for the synthesis of optically pure hydrazino acids and efficient incorporation of hydrazino building blocks into peptide sequence hamper wider exploitation of hydrazino peptidomimetics. Here we described the utility of Nα-benzyl protected and unprotected hydrazino derivatives of natural α-amino acids in synthesis of peptidomimetics. While incorporation of Nα-benzyl-hydrazino acids into peptide chain and deprotection of benzyl moiety proceeded with difficulties, unprotected hydrazino acids allowed fast and simple construction of hybrid peptidomimetics.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-015-1288-9) contains supplementary material, which is available to authorized users.

Highlights

Proteins and their conjugates are key players in fundamental molecular functions that define life as we know
Intervention into peptide backbone by incorporation of non-natural amino acids or replacement of peptide bond with isosteres has a major implication on peptidomimetic properties
We present here our findings on synthesis of di- and tripeptides with embedded hydrazino acids derived from natural amino acids

Summary

Introduction

Proteins and their conjugates are key players in fundamental molecular functions that define life as we know. N-terminally protected dipeptides were obtained by the following procedure: Boc-Aaa-OH (Aaa = Leu, Val, Ala) (1 mmol) and HOSu (1.5 mmol) were dissolved in dry DMF (3 mL) and solution cooled down to 0 °C.

Results

Conclusion