PEGylation of octreotide using an alpha,beta-unsaturated-beta-mono-sulfone functionalized Peg reagent

PEGylation is a well-established technique utilized to overcome the problems related to the therapeutic applications of pep tides and proteins. Reasons for the PEGylation of these biological macromolecules include reducing immunogenicity, proteolytic degradation and rapid clearance from blood circulation. Octreotide is an octapeptide analogue of naturally-occurred somatostatin. This peptide has elimination half-life of less than 2 h that requires frequent daily subcutaneous or intravenous administration. To address this issue, octreotide modification was investigated using bis-thiol alkylating PEG reagent. The required bisthiol alkylating reagent [V] was prepared from commercially available 4-acetyl benzoic acid in five steps. Octreotide disulfide bond was mildly reduced to liberate the two cysteine sulfur atoms followed by bis-alkylation to form PEGylated peptide. The PEG modification process was monitored through the reverse phase HPLC and 'H-NMR analysis. According to the HPLC chromatograms of PEGylation reaction, the peak with 30 min retention time was identified to be PEG-octreotide. In addition, H-NMR analysis showed a 7.44% degree of PEG substitution

Design and synthesis of new imidazole derivatives of captopril

A new series of alkylthio imidazole analogues of captopril, an ACE inhibitor used in the treatment of hypertension, was designed and synthesized in order to obtain agents more active than captopril with less side effects. All the compounds thus prepared were purified and characterized by IR, NMR and Mass analytical instruments