Academic literature on the topic 'Peptide models; Hydrolytic process'

Among the genetically encoded amino acid residues, methionine (Met) and cysteine (Cys) are special because they each contain an atom of sulphur. The present chapter describes how these residues are incorporated into peptides in the context of an Fmoc/tBu solid-phase synthesis strategy, as well as further considerations once the synthetic peptide is released from the support. Of added interest, some manipulations of Cys are advantageously performed at the level of the assembled peptide-resin, prior to cleavage. Many of the aspects discussed here also carry over to the preparation of peptides using a Boc/Bzl strategy. The major problems associated with management of Met reflect the susceptibility of the thioether to alkylation and oxidation. One of the merits of the Fmoc/tBu strategy, in contrast to Boc/Bzl, is that in the former strategy Met is usually introduced without recourse to a protecting group for the thioether side-chain. As documented in this chapter, a proper understanding of acidolytic cleavage conditions and the availability of selective procedures to reverse any inadvertent oxidation are likely to lead to success in obtaining homogeneous peptides containing Met. Management of Cys provides additional significant challenges. For some targets, Cys is required with its side-chain in the free thiol form, whereas for other targets, an even number of Cys residues pair with each other via disulphide linkage(s) to provide cystine residue(s). Disulphide bridges play an important role in the folding and structural stabilization of many natural peptides and proteins, and their artificial introduction into natural or designed peptides is a useful approach to improve biological activities/specificities and stabilities. Furthermore, use of a disulphide bridge is a preferred method to conjugate peptides to protein carriers for increasing the response in immuno-logical studies, to link two separate chains for developing discontinuous epitopes, and to generate active site models. This chapter describes Cys protecting groups, how they are removed to provide either free thiols or disulphides directly, and various strategies and practical considerations to minimize side reactions and maximize formation of the desired products. The thioether side-chain of Met is subject to alkylation and oxidation side reactions, either during the synthetic process or during subsequent handling of the Met-containing peptide.

Proteins are nature’s nano-robots in the form of functional molecular components of living cells. The function of these natural nano-robots often requires conformational transitions between two or more native conformations that are made possible by the intrinsic mobility of the proteins. Understanding these transitions is essential to the understanding of how proteins function, as well as to the ability to design and manipulate protein-based nano-mechanical systems [1]. Modeling protein molecules as kinematic chains provides the foundation for developing powerful approaches to the design, mani

Modeling protein molecules as kinematic chains provides the foundation for developing powerful approaches to the design, manipulation and fabrication of peptide based molecules and devices. Nevertheless, these models possess a high number of degrees of freedom (DOF) with considerable computational implications. On the other hand, real protein molecules appear to exhibits a much lower mobility during the folding process than what is suggested by existing kinematic models. The key contributor to the lower mobility of real proteins is the formation of Hydrogen bonds during the folding process. In