Influence of α-MSH terminal amino acids on binding affinity and biological activity in melanoma cells

Sahm, U.G.; Olivier, George; Branch, Sarah K.; Moss, S. H.; Pouton, Colin W.

doi:10.1016/0196-9781(94)90202-x

Cited by 22 publications

(13 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The peculiarities of MSH dictated its localization at the C terminus of MRTs: only the N terminus of the hormone can be modified without loss of MSH activity/binding to its receptors (31,32). The MSH gene was prepared synthetically using codons optimized for expression in E. coli.…”

Section: Design Of Modular Plasmids Encoding Mrts Of Pss Synthesis mentioning

confidence: 99%

“…As mentioned above, MSH was chosen as the ligand module conferring recognition by specific target cells (melanoma) through binding to melanocortin receptors with subsequent internalization (30). The peculiarities of MSH dictated its localization at the C terminus of MRTs: only the N terminus of the hormone can be modified without loss of MSH activity/binding to its receptors (31,32). The MSH gene was prepared synthetically using codons optimized for expression in E. coli.…”

Section: Design Of Modular Plasmids Encoding Mrts Of Pss Synthesis mentioning

confidence: 99%

See 1 more Smart Citation

Recombinant modular transporters for cell‐specific nuclear delivery of locally acting drugs enhance photosensitizer activity

Rosenkranz¹,

Лунин²,

Gulak³

et al. 2003

FASEB j.

View full text Add to dashboard Cite

The search for new pharmaceuticals that are specific for diseased rather than normal cells in the case of cancer and viral disease has raised interest in locally acting drugs that act over short distances within the cell and for which different cell compartments have distinct sensitivities. Thus, photosensitizers (PSs) used in anti-cancer therapy should ideally be transported to the most sensitive subcellular compartments in order for their action to be most pronounced. Here we describe the design, production, and characterization of the effects of bacterially expressed modular recombinant transporters for PSs comprising 1) alpha-melanocyte-stimulating hormone as an internalizable, cell-specific ligand; 2) an optimized nuclear localization sequence of the SV40 large T-antigen; 3) an Escherichia coli hemoglobin-like protein as a carrier; and 4) an endosomolytic amphipathic polypeptide, the translocation domain of diphtheria toxin. These modular transporters delivered PSs into the nuclei, the most vulnerable sites for the action of PSs, of murine melanoma cells, but not non-MSH receptor-overexpressing cells, to result in cytotoxic effects several orders of magnitude greater than those of nonmodified PSs. The modular fusion proteins described here for the first time, capable of cell-specific targeting to particular subcellular compartments to increase drug efficacy, represent new pharmaceuticals with general application.

show abstract

Section: Design Of Modular Plasmids Encoding Mrts Of Pss Synthesis mentioning

confidence: 99%

Section: Design Of Modular Plasmids Encoding Mrts Of Pss Synthesis mentioning

confidence: 99%

Recombinant modular transporters for cell‐specific nuclear delivery of locally acting drugs enhance photosensitizer activity

Rosenkranz¹,

Лунин²,

Gulak³

et al. 2003

FASEB j.

View full text Add to dashboard Cite

show abstract

“…The influence of single amino acid replacements by Ala on the binding affinity and biological activity of α ‐MSH utilizing B16 murine melanoma cells (putative MC1R) (11), and more recently γ ‐MSH (Tyr 1 ‐Val 2 ‐Met 3 ‐Gly 4 ‐His 5 ‐Phe 6 ‐Arg 7 ‐Trp 8 ‐Asp 9 ‐Arg 10 ‐Phe 11 ‐Gly 12 ‐OH) utilizing the cloned human MC3R‐MC5R (18) has been studied systematically. An Ala scan of α ‐MSH in the B16 mouse melanoma cells revealed that the three terminal amino acids at both the C‐ and N‐terminal were not necessary for binding or activity (19). The core sequence of residues 4–9 ( α ‐MSH numbering) was required for receptor binding and triggering a biological response.…”

Section: Introductionmentioning

confidence: 99%

Modified melanocortin tetrapeptide Ac‐His‐dPhe‐Arg‐Trp‐NH₂ at the arginine side chain with ureas and thioureas

Joseph¹,

Sorensen²,

Wood³

et al. 2005

The Journal of Peptide Research

View full text Add to dashboard Cite

The Ac-His-dPhe-Arg-Trp-NH2 tetrapeptide is a nonselective melanocortin agonist and replacement of Arg in the tetrapeptide with acidic, basic or neutral amino acids results in reduced potency at the melanocortin receptor (MCR) isoforms (MC1R and MC3-5R). To determine the importance of the positive charge and the guanidine moiety for melanocortin activity, a series of urea- and thiourea-substituted tetrapeptides were designed. Replacement of Arg with Lys or ornithine reduced agonist activity at the mouse mMC1 and mMC3-5 receptors, thus supporting the hypothesis that the guanidine moiety is important for receptor potency, particularly at the MC3-5 receptors. The Arg side chain-modified tetrapeptides examined in this study include substituted phenyl, naphthyl, and aliphatic urea and thiourea residues using a Lys side-chain template. These ligands elicit full-agonist pharmacology at the mouse MCRs examined in this study.

show abstract

“…Quantitative receptor-binding assays were carried out following a previously described method (28,29). Cells were seeded at a density of 5 ϫ 10 5 cells per well in 24-well tissue culture plates and exposed to various concentrations of peptides in 0.5 ml of binding media (25 mM Hepes͞NaOH, pH 7.4͞0.2% BSA͞0.3 mM 1, 10-phenanthroline͞Ϸ100,000 cpm of 125 ]-␣-MSH in 100 l of saline solution subcutaneously between the scapulae 30 min prior to the injection of 99m TcCCMSH.…”

Section: Synthesis and Purification Of Peptide-metal Complexesmentioning

confidence: 99%

Design and characterization of α-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination

Giblin

Wang

Hoffman

et al. 1998

Proc. Natl. Acad. Sci. U.S.A.

124

198

View full text Add to dashboard Cite

Metal ions often play critical roles in protein structure and function. Engineered metal-binding sites in peptides and proteins have been widely used to enhance structural integrity, stabilize biologically active conformations, and confer novel enzymatic activities (1-3). Biochemical and structural analyses of transition-metal coordination by proteins and peptides have traditionally focused on zinc, copper, manganese, and iron because of their roles in important biological processes (4-7). Other transition metals not found in natural proteins have coordination, isotopic, and chemical properties that make them attractive for peptide and protein engineering. Rhenium (Re) and technetium (Tc) are group VIIB transition metals that share similar coordination geometries and form stable complexes with amine and amide nitrogens, carboxylate oxygens, and thiolate and thioether sulfurs, with a strong preference for thiolate sulfurs (8). Radioactive isotopes of Re and Tc have significant medical applications because of the nature of their associated radiation and physical half-life properties.The synthesis and characterization of radiolabeled antibodies, peptides, and steroid hormones as in vivo tumor-imaging and therapeutic agents is an active area of cancer research today. These molecules specifically target tumor cells by virtue of their high specificities for receptors and antigens present on the surfaces of these cells. In one commonly used approach, metallic radionuclides such as 186 Re, 188

show abstract

Influence of α-MSH terminal amino acids on binding affinity and biological activity in melanoma cells

Cited by 22 publications

References 13 publications

Recombinant modular transporters for cell‐specific nuclear delivery of locally acting drugs enhance photosensitizer activity

Recombinant modular transporters for cell‐specific nuclear delivery of locally acting drugs enhance photosensitizer activity

Modified melanocortin tetrapeptide Ac‐His‐dPhe‐Arg‐Trp‐NH₂ at the arginine side chain with ureas and thioureas

Design and characterization of α-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination

Contact Info

Product

Resources

About

Influence of α-MSH terminal amino acids on binding affinity and biological activity in melanoma cells

Cited by 22 publications

References 13 publications

Recombinant modular transporters for cell‐specific nuclear delivery of locally acting drugs enhance photosensitizer activity

Recombinant modular transporters for cell‐specific nuclear delivery of locally acting drugs enhance photosensitizer activity

Modified melanocortin tetrapeptide Ac‐His‐dPhe‐Arg‐Trp‐NH2 at the arginine side chain with ureas and thioureas

Design and characterization of α-melanotropin peptide analogs cyclized through rhenium and technetium metal coordination

Contact Info

Product

Resources

About

Modified melanocortin tetrapeptide Ac‐His‐dPhe‐Arg‐Trp‐NH₂ at the arginine side chain with ureas and thioureas