Functional Modification of Thioether Groups in Peptides, Polypeptides, and Proteins

Abstract

Recent developments in the modification of methionine and other thioether containing residues in peptides, polypeptides and proteins are reviewed. Properties and potential applications of the resulting functionalized products are also discussed. While much of this work is focused on natural Met residues, modifications at other side-chain residues have also emerged as new thioether containing amino acids have been incorporated into peptidic materials. Functional modification of thioether containing amino acids has many advantages, and is complimentary methodology to the widely utilized methods for modification at cysteine residues.

Oxidation‐Responsive Materials: Biological Rationale, State of the Art, Multiple Responsiveness, and Open Issues

“…Methionine‐Based Artificial Constructs (Peptides/Proteins) : Deming has recently reviewed the field of methionine‐based polypeptidic structures, which can be modified via sulfur oxidation or alkylation . Here we would like to emphasize a morphological consequence of Met oxidation in such typically highly ordered structures: the higher hydrophilicity of oxidized species is typically accompanied by a loss of order in their secondary structure.…”

Tunable, Functional Diblock Copolypeptide Hydrogels Based on Methionine Homologs

“…The objective of this study was the preparation of diblock copolypeptides that utilize homologs of l ‐methionine as precursors to a variety of different functional DCH ( Scheme 1 ). l ‐Methionine residues are emerging as versatile components of biomimetic polypeptide materials since they can be readily modified in different ways with both high selectivity and high conversion . These modifications also mimic natural l ‐methionine biochemical processes, that is, oxidation and alkylation reactions .…”

“… l ‐Methionine residues are emerging as versatile components of biomimetic polypeptide materials since they can be readily modified in different ways with both high selectivity and high conversion . These modifications also mimic natural l ‐methionine biochemical processes, that is, oxidation and alkylation reactions . For example, l ‐methionine sulfoxide residues in proteins are a natural product of oxidative stress within cells and tissues, and hydrophobic poly( l ‐methionine), M, can likewise be oxidized to give non‐ionic, hydrophilic, and minimally toxic poly( l ‐methionine sulfoxide), M O .…”

“…For example, l ‐methionine sulfoxide residues in proteins are a natural product of oxidative stress within cells and tissues, and hydrophobic poly( l ‐methionine), M, can likewise be oxidized to give non‐ionic, hydrophilic, and minimally toxic poly( l ‐methionine sulfoxide), M O . Alkylation of l ‐methionine residues using a variety of reagents also mimics the natural products S‐methyl‐ l ‐methionine and S‐adenosyl‐ l ‐methionine, and provides a means to convert hydrophobic l ‐methionine to hydrophilic poly(S‐alkyl‐ l ‐methionine sulfonium), M R , functionalized polypeptides . Our group has developed and utilized these methods to prepare l ‐methionine‐based functional copolypeptide vesicles and hydrogels …”

“…We also wanted to evaluate if these homologs provide a means to adjust DCH properties via their differences in side‐chain length. These homologs possess the same thioether functionality found in l ‐methionine, and so it was expected they could be modified using the same alkylation or oxidation methods . To form DCH, the thioether groups in l‐ homomethionine and l‐ 6‐(methylthio)‐ l‐ norleucine copolypeptides were alkylated using a variety of epoxides, giving the corresponding sulfonium derivatives bearing different functional groups .…”