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Screening of synthetic phage display scFv libraries yields competitive ligands of human leptin receptor.
Biochem Biophys Res Commun 2014; 452(3):479-83BB

Abstract

Initially considered the main endogenous anorexigenic factor, fat-derived leptin turned out to be a markedly pleiotropic hormone, influencing diverse physiological processes. Moreover, hyperleptinemia in obese individuals has been linked to the onset or progression of serious disorders, such as cancer, autoimmune diseases, and atherosclerosis, and antagonizing peripheral leptin's signalization has been shown to improve these conditions. To develop an antibody-based leptin antagonist we have devised a tailored panning procedure and screened two phage display libraries of single chain variable antibody fragments (scFvs) against recombinant leptin receptor. One of the scFvs was expressed in Escherichia coli and its interaction with leptin receptor was characterized in more detail. It was found to recognize a discontinuous epitope and to compete with leptin for receptor binding with IC50 and Kd values in the nanomolar range. The reported scFv represents a lead for development of leptin antagonists that may ultimately find use in therapy of various hyperleptinemia-related disorders.

Authors+Show Affiliations

University of Ljubljana, Faculty of Pharmacy, Department of Pharmaceutical Biology, Aškerčeva 7, SI-1000 Ljubljana, Slovenia. Electronic address: peter.molek@ffa.uni-lj.si.University of Ljubljana, Faculty of Pharmacy, Department of Pharmaceutical Biology, Aškerčeva 7, SI-1000 Ljubljana, Slovenia. Electronic address: miha.vodnik@ffa.uni-lj.si.University of Ljubljana, Faculty of Pharmacy, Department of Pharmaceutical Biology, Aškerčeva 7, SI-1000 Ljubljana, Slovenia; Jožef Stefan Institute, Department of Biotechnology, Jamova 39, SI-1000 Ljubljana, Slovenia. Electronic address: borut.strukelj@ffa.uni-lj.si.University of Ljubljana, Faculty of Pharmacy, Department of Pharmaceutical Biology, Aškerčeva 7, SI-1000 Ljubljana, Slovenia. Electronic address: tomaz.bratkovic@ffa.uni-lj.si.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25159846

Citation

Molek, Peter, et al. "Screening of Synthetic Phage Display scFv Libraries Yields Competitive Ligands of Human Leptin Receptor." Biochemical and Biophysical Research Communications, vol. 452, no. 3, 2014, pp. 479-83.
Molek P, Vodnik M, Strukelj B, et al. Screening of synthetic phage display scFv libraries yields competitive ligands of human leptin receptor. Biochem Biophys Res Commun. 2014;452(3):479-83.
Molek, P., Vodnik, M., Strukelj, B., & Bratkovič, T. (2014). Screening of synthetic phage display scFv libraries yields competitive ligands of human leptin receptor. Biochemical and Biophysical Research Communications, 452(3), pp. 479-83. doi:10.1016/j.bbrc.2014.08.087.
Molek P, et al. Screening of Synthetic Phage Display scFv Libraries Yields Competitive Ligands of Human Leptin Receptor. Biochem Biophys Res Commun. 2014 Sep 26;452(3):479-83. PubMed PMID: 25159846.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Screening of synthetic phage display scFv libraries yields competitive ligands of human leptin receptor. AU - Molek,Peter, AU - Vodnik,Miha, AU - Strukelj,Borut, AU - Bratkovič,Tomaž, Y1 - 2014/08/23/ PY - 2014/08/12/received PY - 2014/08/19/accepted PY - 2014/8/28/entrez PY - 2014/8/28/pubmed PY - 2015/2/26/medline KW - Antagonist KW - Antibody KW - Leptin KW - Phage display KW - Receptor KW - scFv SP - 479 EP - 83 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 452 IS - 3 N2 - Initially considered the main endogenous anorexigenic factor, fat-derived leptin turned out to be a markedly pleiotropic hormone, influencing diverse physiological processes. Moreover, hyperleptinemia in obese individuals has been linked to the onset or progression of serious disorders, such as cancer, autoimmune diseases, and atherosclerosis, and antagonizing peripheral leptin's signalization has been shown to improve these conditions. To develop an antibody-based leptin antagonist we have devised a tailored panning procedure and screened two phage display libraries of single chain variable antibody fragments (scFvs) against recombinant leptin receptor. One of the scFvs was expressed in Escherichia coli and its interaction with leptin receptor was characterized in more detail. It was found to recognize a discontinuous epitope and to compete with leptin for receptor binding with IC50 and Kd values in the nanomolar range. The reported scFv represents a lead for development of leptin antagonists that may ultimately find use in therapy of various hyperleptinemia-related disorders. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/25159846/Screening_of_synthetic_phage_display_scFv_libraries_yields_competitive_ligands_of_human_leptin_receptor_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(14)01510-1 DB - PRIME DP - Unbound Medicine ER -