We describe a novel chemoenzymatic synthesis of eel calcitonin (eCT) glycopeptide analogues having natural N-linked oligosaccharides, such as a disialo biantennary complex-type [(NeuAc-Gal-GlcNAc-Man)2-Man-GlcNAc2], an asialo complex-type [(Gal-GlcNAc-Man)2-Man-GlcNAc2], and a high-mannose type [Man6-GlcNAc2] as model compounds for glycoprotein synthesis. First, a glycoprotein containing N-acetylglucosamine (GlcNAc) was prepared by a chemical synthesis. Next, natural oligosaccharides were added to the prepared glycopeptide containing GlcNAc by a transglycosylation reaction using endo-β-N-acetylglucosaminidase (endo-β-GlcNAc-ase) from Mucor hiemalis.

Synthesis of a Glycopeptide Containing Oligosaccharides: Chemoenzymatic Synthesis of Eel Calcitonin Analogues Having Natural N-Linked Oligosaccharides

Five human breast cancer cell lines (MCF 7, T 47D, BT 20, MDA 157, and MDA 231) and a human breast epithelial cell line (HBL 100) have been found to contain specific high-affinity receptors for 1,25-dihydroxyvitamin D3, Kd values ranged from 0.6 to 2.0 X 10(-11) M and receptor concentration from 31 to 150 fmol/mg cytosol protein. Two of the breast cancer lines (MCF 7 and T 47D) contain specific high-affinity receptors for calcitonin and a calcitonin-responsive adenylate cyclase, which have been characterized with the aid of salmon, eel, and human calcitonins and in several substituted analogues of human calcitonin. The 1,25-dihydroxyvitamin D3 receptor may reflect a normal property of the breast cell. Breast cancer cell lines provide a useful source of 1,25-dihydroxyvitamin D3 receptors. Their coexistence with a calcitonin receptor and biological response in some breast cancers offers the opportunity to investigate new aspects of breast cancer endocrinology.

https://cancerres.aacrjournals.org/content/canres/40/12/4764.full.pdf

Calcitonin and 1,25-Dihydroxyvitamin D3 Receptors in Human Breast Cancer Cell Lines

The calcitonin/CGRP multigene complex encodes a family of peptides: calcitonin, its C-terminal flanking peptide, katacalcin, and a third novel peptide, calcitonin gene-related peptide (CGRP). The 32-amino acid peptide calcitonin inhibits the osteoclast, thereby conserving skeletal mass during periods of potential calcium lack, such as pregnancy, growth, and lactation. This hormonal role is emphasized by observations that lower circulating calcitonin levels are associated with bone loss and that calcitonin replacement prevents further bone loss. Structurally, CGRP resembles calcitonin and has been implicated in neuromodulation and in the physiological regulation of blood flow. Here we review the molecular genetics, structure, and function of the calcitonin-gene peptides as analyzed in the laboratory and focus on more recent clinical studies relating to disorders and therapeutics.

The Calcitonin Gene Peptides: Biology and Clinical Relevance

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840200313

Parenteral calcitonin for metabolic bone disease associated with primary biliary cirrhosis

Calcitonin was discovered over 50 yr ago as a new hormone that rapidly lowers circulating calcium levels. This effect is caused by the inhibition of calcium efflux from bone, as calcitonin is a pot...

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The Activity of Peptides of the Calcitonin Family in Bone

Eel-calcitonin and its [Asu1,7]-analog, deamino-dicarba-analog, were synthesized by the conventional solution method. The natural-type product showed 4300 MRC U/mg in the hypocalcemic potency which was comparable to that of the natural hormone isolated from eel. Hormonal activity of the Asu-analog was also as high as 3400 MRC U/mg.

T. Morikawa

Papers

Synthesis of eel-calcitonin and (asu1,7)-eel-calcitonin: contribution of the disulfide bond to the hormonal activity.