Date Approved

8-2013

Date Posted

9-19-2013

Degree Type

Open Access Thesis

Degree Name

Master of Science (MS)

Department

Chemistry

Committee Member

Deborah Heyl-Clegg, Ph.D, Chair

Committee Member

Jamie Scaglione, Ph.D., Chair

Committee Member

Hedeel Guy Evans, Ph.D.

Abstract

Mycosubtilin is a naturally occurring antifungal obtained from Bacillus subtilis that also displays limited antibiotic activity. Structurally, mycosubtilin is a macrocycliclipoheptapeptide of sequence Asn-Tyr-Asn-Gln-Pro-Ser-Asn, with the N-terminal Asn joined by a β-amino fatty acid. Besides the antifungal and antibiotic activities,these molecules are also hemolytic in nature. Hence, the purpose of this study is to synthesize a potent antifungal analogue of mycosubtilin, with a modified β-amino fatty acid, devoid of any hemolytic activity. A chemoenzymatic approach was used to synthesize the cyclic peptide, which involved the synthesis of the linear peptide chain of desired amino acid sequence, thiophenylderivatization of the peptide at the C-terminus, followed by its enzymatic cyclization using the isolated thioesterase from B. subtilis. Thus far, we have successfully synthesized the analogue of mycosubtilin. Future work will focus on purifying the product and testing it for antifungal and hemolytic activity.

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