Synthesis and structure-activity study of myxoma virus growth factor

Journal Article · Tue Apr 02 04:00:00 EST 1991 · Biochemistry; (United States)

DOI:https://doi.org/10.1021/bi00227a020· OSTI ID:5558053

Lin, Yao-Zhong; Ke, Xiao-Hong; Tam, J P ^[1]

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1. Rockefeller Univ., New York (USA)

Myxoma virus growth factor (MGF) is an 85-residue peptide derived from the gene product of a DNA tumor virus that infects rabbits. The carboxyl domain of MGF possesses about 40% sequence homology with the epidermal growth factor (EGF). This EGF-like domain covering residues 30-83 was synthesized and found to possess putative activities of EGF. It was, however, about 200-fold less active than EGF in the competitive binding of human EGF receptor in A431 cells and the stimulation of ({sup 3}H)thymidine uptake in NRK 49F cells. MGF(30-83) is a basic and a hydrophobic peptide rich in {beta}-sheet structure. These features in MGF tend to promote aggregation, leading to precipitation even in strongly denaturing solutions. Thus, the refolding of MGF was achieved with difficulty and resulted in low yield. To increase the synthetic yield of MGF(30-83), a cluster of acidic amino acids was added to the NH{sub 2}-terminus of MGF(30-83). This approach was found to be effective in minimizing the refolding difficulties and allowed accessibility to the synthesis of analogues in this class of compounds. The relationships of structure and function of MGF were studied by using analogues with point substitution by the corresponding D-amino acid or by Ala at position 44 or 52 and analogues with deletion of basic residues from the amino terminus. Modifications of both the receptor contact and the structural residues greatly reduced the potency of MGF(30-83), and the overall result correlated well with the known structure-activity of the EGF family.

• OSTI ID: 5558053
• Journal Information: Biochemistry; (United States), Journal Name: Biochemistry; (United States) Vol. 30:13; ISSN 0006-2960; ISSN BICHA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALANINES
AMINO ACIDS
ANIMALS
AZINES
BETA DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CHROMATOGRAPHY
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
GROWTH FACTORS
HETEROCYCLIC COMPOUNDS
HYDROGEN COMPOUNDS
INTERMEDIATE MASS NUCLEI
INTERNAL CONVERSION RADIOISOTOPES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
MAN
MEMBRANE PROTEINS
MICROORGANISMS
MITOGENS
NUCLEI
NUCLEOSIDES
NUCLEOTIDES
ODD-EVEN NUCLEI
ONCOGENIC VIRUSES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PARASITES
PRIMATES
PROTEINS
PYRIMIDINES
RADIOISOTOPES
RADIORECEPTOR ASSAY
RECEPTORS
RIBOSIDES
SEPARATION PROCESSES
STRUCTURE-ACTIVITY RELATIONSHIPS
THYMIDINE
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES
VIRUSES