Post-assembly Peptide Modifications by Chemical Methods

Abstract

The demand for peptide drugs is increasing and in this context, "post-assembly (or post-translational) peptide modification strategies" by chemical manipulation of intact oligo-peptides has provided several analogues. Compounds prepared by this method are useful therapeutic molecules for structure activity studies. Herein, we describe various chemical methods such as cross-coupling reactions, cycloaddition reactions, radical reactions and ring-closing metathesis reactions that are useful for post-translational peptide modifications.

Site-Selective C(sp3)–H Functionalization of Di-, Tri-, and Tetrapeptides at the N-Terminus

“… 1 Therefore, postsynthetic modification of peptides has emerged as a significant task of current interests. 4 − 9 For example, the “tag-and-modify” approach has been developed by Davis to covalently modify peptides and proteins through a diverse range of transition metal-catalyzed C–C bond-forming reactions. 6 , 10 Direct C(sp 2 )–H functionalization of inherent phenylalanine and tryptophan moieties has also been elegantly exploited to modify the structures of bioactive small peptides.…”

Diversity-Oriented Approaches to Unusual α-Amino Acids and Peptides: Step Economy, Atom Economy, Redox Economy, and Beyond

“…Next, having developed an RCM approach to cyclic AAA derivatives; the logical extension seems to be the application of these methodologies to peptide modifications involving RCM as a key step . In this regard, we have devised a new postassembly peptide modification strategy involving α, α′-cyclic peptides with restrained conformation by RCM.…”

Expanding the Diversity of Polycyclic Aromatics Through a Suzuki–Miyaura Cross‐Coupling Strategy

“…[40] Since only a limited number of synthetic methods (e.g., BuchererBerg, BB) [41] are available for their preparation, only sim-pler systems are used in this regard. We have selected several constrained analogues of phenylalanine (Phe) -known to be useful in medicinal and bioorganic sciences -for modification, and to demonstrate the utility of SM we have chosen the targets shown in Figure 4.…”

“…In several instances, non-proteinogenic AAAs have been used to modify conformational and stability aspects of native peptides. [40] Among proteinogenic AAAs, Phe is a crucial structural element present in several bioactive peptides, and there are numerous reports in which the replacement of Phe with a constrained analogue generates more effective therapeutics. SM reactions between various arylboronic acids and simple AAA derivatives such as the iodophenylalanine derivative 70 (Scheme 16), obtained from commercially available 4-iodo--phenylalanine (68), have therefore been attempted, and the modified AAAs 71a-g have been obtained in good yields.…”