Abstract

Our objective is to study the structure-activity relationship of corticotropins (ACTHs), lipotropins (LPHs), endorphins (EPs), melanotropins (MSHs) and related peptides. It is planned to isolate ACTH, Beta-LPH, Beta-EP and related peptides from elephant pituitary glands and to determine their amino acid sequences. Once the structure is known elephant ACTH, Beta-EP and related peptides will be synthesized by the solid-phase method. It is also planned to synthesize dogfish and amphibian ACTHs. When the synthetic peptides become available, their biological properties are investigated. Alphah-ACTH-(7-38) [corticotropin-inhibiting peptide (CIP)], the naturally occurring inhibitor to ACTH, is a weak antagonist. It is hope to synthesize analogs of CIP with higher inhibitory activity. Similarly, it is planned to synthesize analogs of Betah-EP-(1-27), [Beta-EP inhibiting peptide (BetaEIP)], the naturally occurring inhibitor to Beta-EP-induced analgesia, with higher inhibitory activity. For the development of sensitive and specific radioimmunoassays (RIAs) for rat and human Gamma-LPH, it is necessary to synthesize these two Gamma-LPHs by the solid-phase method. ACTH and related peptides are known to exhibit no three dimentional structures in water. It is planned to investigate the presence of a tertiary structure in aqueous solutions of human ACTH, Beta-MSH and Alpha-MSH by difference absorption spectroscopy of enzymic digests of the hormones.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM002907-36
Application #
3267845
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1977-03-01
Project End
1992-02-29
Budget Start
1987-03-01
Budget End
1988-02-29
Support Year
36
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Ruthstein, Sharon; Ji, Ming; Mehta, Preeti et al. (2013) Sensitive Cu2+-Cu2+ distance measurements in a protein-DNA complex by double-quantum coherence ESR. J Phys Chem B 117:6227-30
Cuthbert, B N; Holaday, J W; Meyerhoff, J et al. (1989) Intravenous beta-endorphin: behavioral and physiological effects in conscious monkeys. Peptides 10:729-34
Triscari, J; Nelson, D; Vincent, G P et al. (1989) Effect of centrally and peripherally administered beta-endorphin on food intake in rats. Int J Pept Protein Res 34:358-62
Ramasharma, K; Yamashiro, D; Li, C H (1988) Human follicular gonadotropin releasing peptide analogs. Evaluation of biological (in vitro) and immunological activity. Int J Pept Protein Res 32:419-24
Ho, C L; Ko, J L; Li, C H (1988) Beta-endorphin. Receptor binding and peripheral opioid activities of [Gln8]-, [Trp27]-, and [Tyr31]-analogs. Int J Pept Protein Res 32:74-8
Yu, W H; McCann, S M; Li, C H (1988) Synthetic human seminal alpha-inhibin-92 selectively suppresses follicle-stimulating hormone release in vivo. Proc Natl Acad Sci U S A 85:289-92
Li, C H; Oosthuizen, M M; Chung, D (1988) Isolation and primary structures of elephant adrenocorticotropin and beta-lipotropin. Int J Pept Protein Res 32:573-8
Yamashiro, D; Li, C H (1988) New segment synthesis of alpha-inhibin-92 by the acyl disulfide method. Int J Pept Protein Res 31:322-34
Eggens, U; Bahr, V; Oelkers, W et al. (1987) Effects of beta-lipotropin, beta-endorphin, gamma 2-melanotropin and corticotropin on steroid production by isolated human adrenocortical cells. J Clin Chem Clin Biochem 25:779-83
Yamashiro, D (1987) Preparation and properties of some crystalline symmetrical anhydrides of N alpha-tert.-butyloxycarbonyl-amino acids. Int J Pept Protein Res 30:9-12

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