Notizen: Synthese der Insulinketten und ihre Kombination zu insulinaktiven Präparaten

Meienhofer, Johannes; Schnabel, Eugen; Bremer, H. J.; Brinkhoff, O.; Zabel, Rudolf; Sroka, Werner; Klostermayer, H; Brandenburg, Dietrich; Okuda, Takuo; Zahn, Helmut

doi:10.1515/znb-1963-1223

Cited by 178 publications

(54 citation statements)

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“…This· conclusion is supported by a comparison of the struc ture of a-chymotrypsin with the presumed structure of trypsin (55). The discovery of a biological precursor of insulin in which the correct disulphide bridges are formed (56,57) explains the earlier difficulty in obtaining the synthetic hormone in the correctly folded form (58,59). …”

Section: The Folding Of Protein Moleculesmentioning

confidence: 92%

X-Ray Diffraction Studies of Enzymes

Blow¹,

Steitz²

1970

Annu. Rev. Biochem.

200

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Section: The Folding Of Protein Moleculesmentioning

confidence: 92%

X-Ray Diffraction Studies of Enzymes

Blow¹,

Steitz²

1970

Annu. Rev. Biochem.

200

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“…To obtain sufficient material to investigate its bioactivity in fish, Con-Ins G1 was chemically synthesized. Since the first chemical synthesis in 1963 (20), insulin has remained challenging to synthesize with the correct intra-and intermolecular disulfide bonds. A strategy incorporating a pair of selenocysteines in the A chain was used to synthesize Con-Ins G1.…”

Section: The Type Of Insulin Expressed In the Venom Gland Correlates mentioning

confidence: 99%

Specialized insulin is used for chemical warfare by fish-hunting cone snails

Safavi-Hemami

Gajewiak

Karanth

et al. 2015

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

143

173

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More than 100 species of venomous cone snails (genus Conus) are highly effective predators of fish. The vast majority of venom components identified and functionally characterized to date are neurotoxins specifically targeted to receptors, ion channels, and transporters in the nervous system of prey, predators, or competitors. Here we describe a venom component targeting energy metabolism, a radically different mechanism. Two fish-hunting cone snails, Conus geographus and Conus tulipa, have evolved specialized insulins that are expressed as major components of their venoms. These insulins are distinctive in having much greater similarity to fish insulins than to the molluscan hormone and are unique in that posttranslational modifications characteristic of conotoxins (hydroxyproline, γ-carboxyglutamate) are present. When injected into fish, the venom insulin elicits hypoglycemic shock, a condition characterized by dangerously low blood glucose. Our evidence suggests that insulin is specifically used as a weapon for prey capture by a subset of fish-hunting cone snails that use a net strategy to capture prey. Insulin appears to be a component of the nirvana cabal, a toxin combination in these venoms that is released into the water to disorient schools of small fish, making them easier to engulf with the snail's distended false mouth, which functions as a net. If an entire school of fish simultaneously experiences hypoglycemic shock, this should directly facilitate capture by the predatory snail.insulin shock | cone snails | conotoxins | nirvana cabal | venom

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“…My team comprising Meienhofer, Schnabel, Brandenburg, Klostermeyer, Okuda, Zabel, Sroka and Bremer [6] was the first to achieve the combination of synthetic A and B chains of insulin with biologically active material.…”

Section: Synthesis Of Insulinmentioning

confidence: 99%

“…In spite of extensive coverage of the history of the various insulin syntheses, people still wonder why the first chemical synthesis [6] was achieved in the German Wool Textile Research Institute in Aachen.…”

Section: Introductionmentioning

confidence: 99%