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Engineering Disulphide Bonds Among HBD-3 : Modified Analogs

There has been increasing interest in the study of defensins as these cysteine-rich cationic peptides display a board spectrum of anti-microbial activity. However, these small peptides are also cytotoxic towards eukaryotic cells. Therefore, newer defensin derivaties with greater antimicrobial activity and minimal cytotoxicity are constantly being designed. Of the three beta-defensins found in the human body, HBD-3 has been reported to be most potent. The characteristic of HBD-3 to form dimers in the solution might be the reason for its enhanced potency. In this study, previously synthesised analogs of HBD-3 were used to investigate this claim. Modifications were made to these analogs to allow a disulphide bond to be formed between 2 of the analogs making a dimer. Common oxidizing agents such as potassium ferricyanide, iodine and dimethyl sulphoxide (DMSO) were used to form the disulphide bond among the modified analogs to obtain the dimer. Among the three, only DMSO was successful in forming the disulphide bond effectively. Out of the 6 modified analogs studied, the DMSO oxidation procedure was able to form dimers in 5 of the modified analogs. Successfully formed analog dimers would then be used for cytotoxicity and antimicrobial studies.

Student: De Souza Andrew Nigel (Diploma in Biomedical Science)

Supervisor: Dr Zhou Lei, Dr Liu Shou Ping (Singapore Eye Research Institute)

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