From Glycopeptides to Glycopeptoids

Abstract

This review covers the published literature describing the synthesis of glycopeptoids, a family of glycopeptide mimics. Members of this family are composed of an N‐substituted glycine or β‐alanine oligomer backbone linked to one or several carbohydrate moieties at the amide nitrogen atoms. The interest in this class of biomimetics lies in their enhanced proteolytic stability and greater conformational flexibility relative to glycopeptides. This Microreview not only describes the different methods for synthesising glycopeptoids but also discusses their application both as glycopeptidomimetics and glycocluster constructs.

Iminosugar‐Cyclopeptoid Conjugates Raise Multivalent Effect in Glycosidase Inhibition at Unprecedented High Levels

“…Cyclopeptoids appear as ideal tools to both push and precisely probe the limits of multivalent effects . In contrast to most scaffolds, they indeed offer synthetic flexibility, allowing the access to clusters with finely incremented valencies . Another challenge associated with high‐valency systems is that steric crowding of neighboring ligands may limit the multivalent glycosidase binding .…”

“…[12,13] In contrastt om ost scaffolds,t hey indeed offer synthetic flexibility,a llowing the access to clusters with finely incremented valencies. [14,15] Another challenge associated with high-valency systems is that steric crowding of neighboring ligands may limit the multivalent glycosidase binding. [10,11,16] This effect was expected to be overcome by the fact that, in the designed cyclopeptoid-based clusters, the scaffold size grows with the valency (Scheme1).…”

Advances in Development of Antimicrobial Peptidomimetics as Potential Drugs

“…Besides being promising antimicrobial agents, peptoids with activity against fungi [ 148 ], Candida biofilm [ 149 ], tuberculosis [ 150 ], the neglected tropical disease leishmaniasis [ 151 ], and cancer cells [ 152 ] have been reported. Peptoids have also found applications within supra- and macromolecular engineering [ 153 ], biomaterials [ 145 ], protein peptoid mutagenesis [ 154 ], and as fluorescent analogs for study of delivery to the cell nucleus [ 155 ], Huntington’s disease [ 156 ], positron emission tomography (PET) [ 157 ], glycopeptoids [ 158 ], DNA-binding peptoids [ 159 ], and carboxyalkyl peptoid PNAs [ 160 ].…”

Sugar γ‐Amino Acids as Building Blocks for the Synthesis of Cyclic Neoglycopeptides.

“…Indeed, linear peptides usually show low metabolic stability limiting their use as drugs and display conformational flexibility reducing the strength of the ligand-target binding. [1][2][3][4][5][6] Therefore, the development of original cyclopeptide-based therapeutics is currently a growing interest. Some of them like the wellknown vancomycin and its derivatives, [6,7] gramicidin, [8,9] colistin, [10] octreotide, [11] and RGD (Arg-Gly-Asp) derivatives [12,13] exhibit useful biological properties as antibiotics, anticancer drugs and integrin inhibitors.…”

“…Cyclic peptides are naturally occurring substances exhibiting improved properties compared to the linear ones. Indeed, linear peptides usually show low metabolic stability limiting their use as drugs and display conformational flexibility reducing the strength of the ligand‐target binding . Therefore, the development of original cyclopeptide‐based therapeutics is currently a growing interest.…”