Sugar Amino Acids and Their Uses in Designing Bioactive Molecules

Abstract

In search of new molecular entities for discovering new drugs and materials, organic chemists are looking for innovative approaches that try to imitate nature in assembling quickly large number of distinct and diverse molecular structures from 'nature-like' and yet unnatural designer building blocks using combinatorial approach. The main objective in developing such libraries is to mimic the diversities displayed in structures and properties of natural products. The unnatural building blocks used in these assemblies are carefully designed to manifest the structural diversities of the monomeric units used by nature like amino acids, carbohydrates and nucleosides to build its arsenal. Compounds made of such unnatural building blocks are also expected to be more stable toward proteolytic cleavage in physiological systems than their natural counterparts. Sugar amino acids constitute an important class of such polyfunctional scaffolds where the carboxyl, amino and hydroxyl termini provide an excellent opportunity to organic chemists to create structural diversities akin to nature's molecular arsenal. Recent advances in the area of combinatorial chemistry give an unprecedented technological support for rapid compilations of sugar amino acid-based libraries exploiting the diversities of carbohydrate molecules and well-developed solid-phase peptide synthesis methods. This review describes the development of sugar amino acids as a novel class of peptidomimetic building blocks and their applications in creating large number of structurally diverse peptide-based molecules many of which display interesting three-dimensional structures as well as useful biological properties.

A Conformationally Locked AminomethylC‐Glycoside and Studies on ItsN‐Pyren‐1‐ylcarbonyl Derivative Inserted into Oligodeoxynucleotides

“…Furthermore, only a few changes in the synthetic strategy enabled the synthesis of the novel, rigid LNA-based linker 12 (Scheme 1). The six-atom linker is suitable for use in solid-phase peptide synthesis, whilst the structural design of the building block contributes to the still expanding family of sugar amino acids (SAAs) [9][10][11] resembling conformationally restrained dipeptide isosters. [12][13][14][15][16][17] Members of this class of SAAs have found application in foldamers, [18,19] host-guest studies, [20] and as turn inducers.…”

Oligomers and peptidomimetics consisting of methyl 3-amino-2,3-dideoxyhexopyranosiduronic acids

“…Family A is characterized by the OH 3 eCO 3 hydrogen bond, created between the hydroxyl and carbonyl groups originating from the same SAA. In turn, family B is characterized by the OH 3 eCO 2 hydrogen bond, created between the hydroxyl group from SAA and the carbonyl group originating from tyrosine. Probably, the latter hydrogen bond enables all of the molecule to be more bent.…”

Carbohydrates in peptide and protein design

“…The latter method was used by Heyns and Paulsen 35 in 1955 for the first synthesis of a SAA, glucosaminuronic acid, by oxidation of glucosamine. Since then, SAAs have been synthesized by Kessler et al, 34 Chakraborty et al, 36,37 Dondoni and Marra, 38 and many others, and include both -, -, and -SAA, as well as both furanoside and pyranoside ring forms (Figure 7). Also, sugar mimetics in which the ring oxygen has been replaced by nitrogen have gained much interest as inhibitors of glucosidases.…”