Publications by authors named "Yiu-Ngok Chan"
In recent years, the conjugation of sugar moieties and lipoamino acids has been extensively investigated as a mean to enhance the stability towards enzymatic degradation and the permeability across biological membranes of poorly orally available drugs, including peptides. In this prospect, a library of novel derivatives of the dipeptide L-Glu-L-Trp, a naturally occurring thymic immunomodulator with high hydrophilic character and low membrane permeability, was designed and synthesised by conjugating 2-amino-dodecanoic acid (C(12)) and/or 1-amino-beta-D-glucuronic acid (GlcAN), beta-D-glucuronic acid (GlcA) and N-beta-D-glucopyranosylamine succinamic acid (GlsNS) residues to the Glu-Trp scaffold, using an Fmoc solid-phase peptide synthesis strategy on trichlorotrityl resin. A cellobiose derivative was also prepared in solution.
View Article and Find Full Text PDFA T cell antigen receptor (TCR) transmembrane sequence derived peptide (CP) has been shown to inhibit T cell activation both in vitro and in vivo at the membrane level of the receptor signal transduction. To examine the effect of sugar or lipid conjugations on CP function, we linked CP to 1-aminoglucosesuccinate (GS), N-myristate (MYR), mono-di-tripalmitate (LP1, LP2, or LP3), and a lipoamino acid (LA) and examined the effects of these compounds on T cell activation in vitro and by using a rat model of adjuvant-induced arthritis, in vivo. In vitro, antigen presentation results demonstrated that lipid conjugation enhanced CP's ability to lower IL-2 production from 56.
View Article and Find Full Text PDFArticle Synopsis
- - The study examined whether lipoamino acid conjugation could enhance the membrane permeability of high-affinity peptides for ryanodine receptors (RyRs) without altering their structure or activity.
- - Results showed that the conjugated peptides significantly increased permeability across cell layers by about 20 times and maintained their essential alpha-helical structure for effective activation of RyRs.
- - Conjugated peptides demonstrated enhanced effectiveness in promoting calcium release compared to unconjugated ones, especially in skeletal muscle, while also showing minimal adverse effects on calcium uptake.
Purpose: To synthesize a number of analogues of Leu-enkephalin with different lipophilicities and to develop an LC-MS method for determining the Caco-2 cell permeability values of these compounds.
Methods: A number of sugar and sugar plus lipoamino acid analogues of Leu-enkephalin were synthesized by solid-phase and solution methods. An LC-MS method was developed for analyzing the Caco-2 cell assay samples and validated against the traditional method using radiolabelled compounds.