Hormone—receptor interactions: Melanotropic activities of covalent serum albumin complexes with α‐melanotropin, α‐melanotropin fragments, and enkephalin

Eberlé, Alex N.; Kriwaczek, V. M.; Schwyzer, R.

doi:10.1016/0014-5793(77)80450-x

Cited by 21 publications

(14 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Eberle et al . coupled α-MSH peptides (six to several hundred) to albumin, thyroglobulin, and tobacco mosaic virus which resulted in 1500-fold higher potency than α-MSH alone [218, 219]. Bivalent ligands were first reported in the clinic by Barb et al .…”

Section: Bivalent and Multivalent Melanocortin Ligandsmentioning

confidence: 99%

See 1 more Smart Citation

Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016

Ericson

Lensing

Fleming

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

The discovery of the endogenous melanocortin agonists in the 1950s have resulted in sixty years of melanocortin ligand research. Early efforts involved truncations or select modifications of the naturally occurring agonists leading to the development of many potent and selective ligands. With the identification and cloning of the five known melanocortin receptors, many ligands were improved upon through bench-top in vitro assays. Optimization of select properties resulted in ligands adopted as clinical candidates. A summary of every melanocortin ligand is outside the scope of this review. Instead, this review will focus on the following topics: classic melanocortin ligands, selective ligands, small molecule (non-peptide) ligands, ligands with sex-specific effects, bivalent and multivalent ligands, and ligands advanced to clinical trials. Each topic area will be summarized with current references to update the melanocortin field on recent progress.

show abstract

Section: Bivalent and Multivalent Melanocortin Ligandsmentioning

confidence: 99%

“…Conjugates of multiple copies α-MSH derivatives to larger biomolecules were reported starting in 1977 [218, 255]. Eberle et al .…”

Section: Bivalent and Multivalent Melanocortin Ligandsmentioning

confidence: 99%

Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016

Ericson

Lensing

Fleming

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

View full text Add to dashboard Cite

show abstract

“…Reaction of TMV-S-MSH' with rabbit anti-u-MSH antisera. The rabbit anti-a-MSH antiserum 2 [21] as well as the antiserum 7, which was obtained in the same way as the antiserum 2 by immunizing rabbits with the complex 1 of [27], were both well-defined and very specific. The control sera were from non-immunized rabbits (gift of Dr. H. G. Kopp).…”

Section: -Mercapto-l-succiny~)-tmv/(i-(bromoaceiyl-d-alanine)3-glycmentioning

confidence: 99%

Tobacco Mosaic Virus as a Carrier for Small Molecules I. The preparation and characterization of a TMV/α‐melanotropin conjugate

Kriwaczek¹,

Eberlé²,

Müller³

et al. 1978

Helvetica Chimica Acta

Self Cite

View full text Add to dashboard Cite

SummaryThe use of tobacco mosaic virus (TMV) covalently loaded with hormones or other small molecules for various purposes including receptor detection and isolation is proposed. The basic principle is that of cooperative affinity interactions involving (large) numbers of artificially introduced sites (e.g. hormones) of the modified virus on the one hand and membrane-bound sites (e.g. receptors) of a cell or of a cellmembrane particle on the other. In order to test the feasibility of such TMV/hormone conjugates, TMV carrying about 500 molecules of a biologically active a -melanotropin analogue was synthesized, and characterized by its aspect under the electron microscope, by its infectivity, its melanophore-stimulating activity, and its reaction with antisera against a -melanotropin. The observed hormonal activity is in accordance with the idea of cooperative affinity interactions.The chemical nature of membrane-bound receptors for drugs and hormones is still an unsolved problem of molecular biology. This paper is the first of a series investigating the use of tobacco mosaic virus (TMV) covalently attached to hormones, drugs, and other comparatively small molecules for the study of receptors. First, some pertinent chemical properties of TMV and of polypeptide-hormone receptors are reviewed and the concept of cooperative affinity labelling is introduced. It is then demonstrated that some 500 molecules of an a-melanotropin (a-MSH) analogue can be covalently attached to the virus particle without destroying the essential chemical and biological properties characteristic of the virus and the hormone. I )This work was supported by the Swiss National Science Foundation. Abbreviations: TMV= tobacco mosaic virus; EM. = electron microscopy; symbols for amino acids and peptides according to the IUPAC-IUB rules [ 11.

show abstract

“…The first examples of a-MSH multivalent constructs consisted of several a-MSH molecules coupled to albumin, thyroglobulin, and tobacco mosaic virus, which displayed a 1,500-fold higher potency than a-MSH alone [32,33]. Further structure-bioactivity studies have demonstrated that enhanced binding affinity could also be achieved with bivalent constructs [34,35].…”

Section: Introductionmentioning

confidence: 97%

Evaluation of novel 99mTc(I)-labeled homobivalent α-melanocyte-stimulating hormone analogs for melanocortin-1 receptor targeting

et al. 2012

View full text Add to dashboard Cite

Aiming to apply the multivalency concept to melanoma imaging, we have assessed the in vivo melanocortin type 1 receptor (MC1R)-targeting properties of (99m)Tc(I)-labeled homobivalent peptide conjugates which contain copies of the α-melanocyte-stimulating hormone (α-MSH) analog [Ac-Nle(4), Asp(5), D-Phe(7), Lys(11)]α-MSH4-11 separated by linkers of different length (L(2) nine atoms and L(3) 14 atoms). The MC1R-binding affinity of L(2) and L(3) is significantly higher than that of the monovalent conjugate L(1). Metallation of these conjugates yielded the complexes fac-[M(CO)(3)(k(3)-L)](+) (M is (99m)Tc/Re; 1/1a, L is L(1); 2/2a, L is L(2); 3/3a, L is L(3)), with IC(50) values in the subnanomolar and nanomolar range. The MC1R-mediated internalization of 2 and 3 is higher than that of 1 in B16F1 melanoma cells. Biodistribution studies in melanoma-bearing mice have shown low nonspecific accumulation with a tumor uptake that correlates with IC(50) values. However, no correlation between tumor uptake and valency was found. Nevertheless, 2 displayed the highest tumor retention, and the best tumor to nontarget organ ratios.

show abstract

Hormone—receptor interactions: Melanotropic activities of covalent serum albumin complexes with α‐melanotropin, α‐melanotropin fragments, and enkephalin

Cited by 21 publications

References 14 publications

Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016

Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016

Tobacco Mosaic Virus as a Carrier for Small Molecules I. The preparation and characterization of a TMV/α‐melanotropin conjugate

Evaluation of novel 99mTc(I)-labeled homobivalent α-melanocyte-stimulating hormone analogs for melanocortin-1 receptor targeting

Contact Info

Product

Resources

About