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PubMed · 7874442

Peptide design using a genetically patterned binary code: growth hormone-releasing hormone as a model.

D A Weigent·B L Clarke·J E Blalock
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Abstract

This paper reviews a method for the design of peptides and proteins of predefined structure and function and provides an example. Specifically, an analog of rat growth hormone-releasing hormone (GHRH) (residues 1-23) was synthesized by solid-phase methods based on a reversed sequence of the mRNA for GHRH (1-23). The new peptide, designated GHRH 3'-5', had a hydropathic profile similar to that of native GHRH 5'-3' (GHRH) but had only 17% primary sequence homology. GHRH 3'-5' specifically bound to the GHRH receptor on rat pituitary cells and to polyclonal anti-GHRH antibody in ELISA and RIA procedures. Additionally, GHRH 3'-5' blocked the in vitro stimulation of GH RNA synthesis and in vitro and in vivo GH release mediated by GHRH. These data show that 3'-5' GHRH with little sequence homology to native rat GHRH is an antagonist and further supports the importance of the linear pattern of hydropathy to the gross secondary and/or tertiary structure and rudimentary function of peptides and proteins. The impact of these findings on the interaction of complementary peptides is discussed.

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Amino Acid SequenceAnimalsAntibodies, MonoclonalBase SequenceCells, CulturedDNA, ComplementaryDrug DesignGrowth HormoneGrowth Hormone-Releasing HormoneMaleMolecular Sequence DataPituitary GlandProteinsRNA, MessengerRadioimmunoassayRadioligand AssayRatsRats, Sprague-DawleyJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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D A Weigent, B L Clarke, J E Blalock. 1994. Peptide design using a genetically patterned binary code: growth hormone-releasing hormone as a model.. https://doi.org/10.1006/immu.1994.1042

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