Carbohydrates in peptide and protein design

Abstract

Monosaccharides and amino acids are fundamental building blocks in the assembly of nature's polymers. They have different structural aspects and, to a significant extent, different functional groups. Oligomerization gives rise to oligosaccharides and peptides, respectively. While carbohydrates and peptides can be found conjoined in nature, e.g., in glycopeptides, the aim of this review is the radical redesign of peptide structures using carbohydrates, particularly monosaccharides and cyclic oligosaccharides, to produce novel peptides, peptidomimetics, and abiotic proteins. These hybrid molecules, chimeras, have properties arising largely from the combination of structural characteristics of carbohydrates with the functional group diversity of peptides. This field includes de novo designed synthetic glycopeptides, sugar (carbohydrate) amino acids, carbohydrate scaffolds for nonpeptidal peptidomimetics of cyclic peptides, cyclodextrin functionalized peptides, and carboproteins, i.e., carbohydrate-based proteinmimetics. These successful applications demonstrate the general utility of carbohydrates in peptide and protein architecture. #

Peptide screening to knockdown Bcl-2's anti-apoptotic activity: Implications in cancer treatment

“…2) were attempted to access their inhibitory efficacy on changing chemical states of termini. It has also been reported that glycopeptides could be used as therapeutic agent to design a vaccine [131] and a novel ligand [132]. Therefore, addition of glucose and deoxyglucose fragments was also considered to make IGD tripeptide specific to tumor cells, which have a high demand for glucose [133].…”

Multivalent display of the antimicrobial peptides BP100 and BP143

“…Carbohydrates are promising candidates as templates for the display of functional groups due to their inherent multifunctionality, the relative rigidity of their structure, and the ease of regioselective chemical manipulation [23–25]. Jensen and co-workers reported the synthesis of carbopeptides and carboproteins bearing several copies of a peptide or a protein tethered in a carbohydrate template.…”

A novel synthetic luteinizing hormone-releasing hormone (LHRH) analogue coupled with modified β-cyclodextrin: Insight into its intramolecular interactions

“…For example, there are certain activated carboxylic derivatives which show enhanced reactivity and selectivity towards the amino than the hydroxyl group. In addition, in literature this synthetic methodology has been successfully applied in other examples where peptides were attached to CDs [19][20][21][22][23][24][25][26][27][28]. Another point of consideration was the short distance between the CD and the peptide if the amino CD derivative is directly attached to glycine.…”

“…In all previously described conjugates of other bioactive peptides with cyclodextrins [19][20][21][22][23][24][25][26][27][28], attachment of the CD unit takes place through the narrow rim of CD. In contrast, molecule 3 described in this work represents an example where a peptide skeleton is attached to CD via the large rim of CD.…”