Multivalent melanotropic peptide and fluorescent macromolecular conjugates

New reagents for characterization of melanotropin receptors

Shubh D. Sharma, Victor J Hruby, Jinwen Jiang, Stanley P L Leong, Mac E. Hadley, Victor J. Hruby

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

Radioreceptor binding studies have documented the presence of melanotropin receptors on some but not all of the various human melanoma cell lines that have been studied. Using a newly developed class of multivalent fluorescent melanotropin-macromolecular conjugates, we have demonstrated for the first time the presence of specific melanotropin receptors on all of the melanoma cell lines, both mouse and human, melanotic as well as amelanotic, that were investigated. The conjugates developed by us consisted of multiple copies of both a potent melanotropin analogue and a fluorophore, both arranged in a pendent fashion on a biologically inert macromolecule. While the multivalency of these conjugates may have established stronger binding with the melanotropin receptors on the cell surface (perhaps by establishing simultaneous multiple interactions), the presence of multiple copies of the fluorophore also greatly increased the level of detection in fluorescence labeling experiments. Membrane receptor-hormone-associated phenomena, such as capping and internalization of the receptor-ligand complex, also were observed. The details of these methods are described using B-16 mouse melanoma cells as a model system. The demonstration of MSH receptors as a common marker for melanoma suggests that this methodology might be employed for early clinical detection and anatomical localization of melanoma. These results also offer the possibility that substitution of the fluorophore in these conjugates by a chemical agent of (chemo-)therapeutic relevance may provide a powerful tool for site specific (tumor) targeting and cytotoxicity.

Original languageEnglish (US)
Pages (from-to)591-601
Number of pages11
JournalBioconjugate Chemistry
Volume5
Issue number6
StatePublished - 1994

Fingerprint

Fluorophores
Peptides
Melanoma
Melanocyte-Stimulating Hormones
Cells
Hormones
Cytotoxicity
Macromolecules
Labeling
Receptor Aggregation
Tumors
Substitution reactions
Demonstrations
Cell Line
Fluorescence
Ligands
Membranes
MSH receptor
Experiments
Neoplasms

ASJC Scopus subject areas

  • Chemistry(all)
  • Organic Chemistry
  • Clinical Biochemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry

Cite this

Multivalent melanotropic peptide and fluorescent macromolecular conjugates : New reagents for characterization of melanotropin receptors. / Sharma, Shubh D.; Hruby, Victor J; Jiang, Jinwen; Leong, Stanley P L; Hadley, Mac E.; Hruby, Victor J.

In: Bioconjugate Chemistry, Vol. 5, No. 6, 1994, p. 591-601.

Research output: Contribution to journalArticle

Sharma, Shubh D. ; Hruby, Victor J ; Jiang, Jinwen ; Leong, Stanley P L ; Hadley, Mac E. ; Hruby, Victor J. / Multivalent melanotropic peptide and fluorescent macromolecular conjugates : New reagents for characterization of melanotropin receptors. In: Bioconjugate Chemistry. 1994 ; Vol. 5, No. 6. pp. 591-601.
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