Biochemistry and Pharmacology - Research Publications

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Author: HOSSAIN, MOHAMMED × Author: Separovic, Frances × Start date: 2010 × Type: Journal Article ×

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    Melittin peptides exhibit different activity on different cells and model membranes
    Jamasbi, E ; Batinovic, S ; Sharples, RA ; Sani, M-A ; Robins-Browne, RM ; Wade, JD ; Separovic, F ; Hossain, MA (SPRINGER WIEN, 2014-12)
    Melittin (MLT) is a lytic peptide with a broad spectrum of activity against both eukaryotic and prokaryotic cells. To understand the role of proline and the thiol group of cysteine in the cytolytic activity of MLT, native MLT and cysteine-containing analogs were prepared using solid phase peptide synthesis. The antimicrobial and cytolytic activities of the monomeric and dimeric MLT peptides against different cells and model membranes were investigated. The results indicated that the proline residue was necessary for antimicrobial activity and cytotoxicity and its absence significantly reduced lysis of model membranes and hemolysis. Although lytic activity against model membranes decreased for the MLT dimer, hemolytic activity was increased. The native peptide and the MLT-P14C monomer were mainly unstructured in buffer while the dimer adopted a helical conformation. In the presence of neutral and negatively charged vesicles, the helical content of the three peptides was significantly increased. The lytic activity, therefore, is not correlated to the secondary structure of the peptides and, more particularly, on the propensity to adopt helical conformation.
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    The Importance of Tryptophan B28 in H2 Relaxin for RXFP2 Binding and Activation
    Chan, LJ ; Wade, JD ; Separovic, F ; Bathgate, RAD ; Hossain, MA (SPRINGER, 2013-03)
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    The C-terminus of the B-chain of human insulin-like peptide 5 is critical for cognate RXFP4 receptor activity
    Patil, NA ; Bathgate, RAD ; Kocan, M ; Ang, SY ; Tailhades, J ; Separovic, F ; Summers, R ; Grosse, J ; Hughes, RA ; Wade, JD ; Hossain, MA (SPRINGER WIEN, 2016-04)
    Insulin-like peptide 5 (INSL5) is an orexigenic peptide hormone belonging to the relaxin family of peptides. It is expressed primarily in the L-cells of the colon and has a postulated key role in regulating food intake. Its G protein-coupled receptor, RXFP4, is a potential drug target for treating obesity and anorexia. We studied the effect of modification of the C-terminus of the A and B-chains of human INSL5 on RXFP4 binding and activation. Three variants of human INSL5 were prepared using solid phase peptide synthesis and subsequent sequential regioselective disulfide bond formation. The peptides were synthesized as C-terminal acids (both A- and B-chains with free C-termini, i.e., the native form), amides (both chains as the C-terminal amide) and one analog with the C-terminus of its A-chain as the amide and the C-terminus of the B-chain as the acid. The results showed that C-terminus of the B-chain is more important than that of the A-chain for RXFP4 binding and activity. Amidation of the A-chain C-terminus does not have any effect on the INSL5 activity. The difference in RXFP4 binding and activation between the three peptides is believed to be due to electrostatic interaction of the free carboxylate of INSL5 with a positively charged residue (s), either situated within the INSL5 molecule itself or in the receptor extracellular loops.