ABSTRACT
An asymmetric synthesis of a 3'-deoxy-3'-18F-fluorothymidine (18F-FLT) precursor has been developed wherein the deoxysugar moiety was synthesized using a novel Ga-mediated allylation of (R)-2,3-cyclohexylideneglyceraldehyde as the key step. The synthesis deviates significantly from the previous syntheses of the 18F-FLT precursors wherein the expensive starting material, thymidine was used.
Subject(s)
Dideoxynucleosides/chemistry , Dideoxynucleosides/chemical synthesis , Chemistry Techniques, Synthetic , StereoisomerismABSTRACT
Here we report the synthesis and study of N-succinyl chitosan based hydrogel beads, stabilized with glycopolymeric network (NSC/Glc-gel) for application in anticancer drug delivery of doxorubicin (DOX). The bio-recognition of lectins by NSC/Glc-gel bead was also studied by UV-vis spectrophotometry. The beads were characterized using FT-IR, SEM and Thermogravimetric analysis. The extent of DOX loading was proportional to the degree of succinylation and the swelling kinetics of the beads showed pH dependency. The beads exhibited sustained release of DOX over a period of more than 15 days in an acidic pH, mimicking the microenvironment of tumor cells, and even lesser release at physiological pH. Release exponent 'n' derived from Korsmeyer-Peppas model implied that NSC88/Glc-gel (88% succinylation of chitosan) beads followed fickian diffusion controlled release mechanism whereas NSC75/Glc-gel (75% succinylation of chitosan) beads follow zero order release profile. The synthesized beads also displayed specificity to lectin Concanavalin A.
Subject(s)
Acrylamides/chemistry , Chitosan/chemistry , Doxorubicin/chemistry , Drug Carriers/chemistry , Hydrogels/chemistry , Acrylamides/chemical synthesis , Animals , Arachis , Cattle , Chitosan/chemical synthesis , Concanavalin A/chemistry , Doxorubicin/administration & dosage , Drug Carriers/chemical synthesis , Hydrogels/chemical synthesis , Hydrogen-Ion Concentration , Microscopy, Electron, Scanning , Peanut Agglutinin/chemistry , Serum Albumin, Bovine/chemistry , Spectroscopy, Fourier Transform Infrared , Surface PropertiesABSTRACT
Side-chain assisted ligation is an auxiliary-mediated ligation strategy in which a thiol bearing cyclohexane or cyclopentane is attached to the side-chain of Asp, Glu, Ser or Thr to function in a similar manner to Cys in a native chemical ligation. Following the ligation step, the auxiliary is removed, without product isolation, under alkaline conditions.
Subject(s)
Amino Acids/chemistry , Peptide Fragments/chemistry , Sulfhydryl Compounds/chemistry , Amino Acid Sequence , Hydrolysis , Molecular Sequence Data , Molecular StructureABSTRACT
The high efficiency and chemoselectivity of peptide ubiquitylation that is achieved using the delta-mercaptolysine prompted us to expand the scope of this residue in various ligation schemes. In this report, we demonstrate the synthesis of five analogues of this important amino acid bearing a variety of protecting groups, which is essential in sequential peptide ligation and ubiquitylation. The key-step in the synthesis is the nucleophilic 1,4-addition of a variety of thiols on a nitro olefin scaffold.
Subject(s)
Amino Acids/chemistry , Amino Acids/chemical synthesis , Peptides/chemistry , Peptides/chemical synthesis , Ubiquitination , Animals , HumansABSTRACT
The utility of a D-glucose-derived aziridine carboxylate was demonstrated for the synthesis of polyhydroxylated quinolizidine and indolizidine alkaloids. The chemoselective reduction of 1 followed by two-carbon homologation by the Wittig reaction afforded gamma,delta-aziridino-alpha,beta-unsaturated ester 9, which on regioselective nucleophilic aziridine ring opening either by using water as a nucleophile or hydrogenation afforded delta-lactams 11/16--true synthons for the synthesis of four structurally different iminosugars, namely quinolizidine alkaloids 5b/5c, swainsonine 6b and lentiginosine 7b analogues. Glycosidase inhibitory activities of these iminosugars were investigated.
