Iodination of insulin in aqueous and organic solvents

Massaglia, A.; Rosa, U.; Rialdi, G.; Rossi, C. A.

doi:10.1042/bj1150011

Cited by 30 publications

(8 citation statements)

References 14 publications

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“…These results contrast with those published by other workers: de Zoeten & de Bruin (1961) and Massaglia et al (1969) concluded that when insulin is iodinated in aqueous solution most of the iodine is substituted into the A-chain residues and that the reactivities ofthe two B-chain residues are similar and low. This difference from our results can be accounted for by the different analytical technique used by these earlier workers, who relied on electrophoretic separation at pH 3.2 of S-sulphonated A and B chains iodinated with radioactive iodine and the measurement of radioactivity in these chains.…”

Section: Results and Discussion Distribution Of Iodine In Iodinated Icontrasting

confidence: 89%

“…We have no evidence to allow us to decide whether A14 or A19 is the critical tyrosine residue in the A chain. However, Massaglia et al (1969) have attributed loss of insulin activity to iodination of residue A19. Also, Blundell et al (1971) point out that residue A19 is tyrosine in all insulin species of known sequence and that it lies amongst an invariant group on the surface of the insulin molecule that could be specifically involved in insulin activity.…”

Section: Single-point-comparison Bioassay Experimentsmentioning

confidence: 99%

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The effect of iodination of particular tyrosine residues on the hormonal activity of insulin

Garratt

Harrison

1972

Biochemical Journal

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Insulin dissolved in aqueous or methanolic buffer was iodinated to give preparations containing an average of between one and five iodine atoms per insulin monomer. The resultant preparations were fragmented in various ways and the ratio of tyrosine to monoiodotyrosine and di-iodotyrosine was determined in each fragment. This has allowed the distribution of iodine between the combined A-chain tyrosine residues and the individual B-chain tyrosine residues to be determined. The hormonal activity of each of these iodinated insulin preparations was measured from their effect on the production of (14)CO(2) from [1-(14)C]glucose by isolated adipose cells. The results were interpreted as meaning that the iodination of tyrosine residue A19 or B16 leads to the inactivation of insulin. Speculations are made about the nature of an interaction between insulin and a receptor site on the target tissue.

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Section: Results and Discussion Distribution Of Iodine In Iodinated Icontrasting

confidence: 89%

Section: Single-point-comparison Bioassay Experimentsmentioning

confidence: 99%

The effect of iodination of particular tyrosine residues on the hormonal activity of insulin

Garratt

Harrison

1972

Biochemical Journal

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“…The position of iodine incorporation into the tyrosine and histidine residues of insulin is not defined in most iodination methods. Variations in conditions may alter the susceptibilities of particular residues for substitution [3][4][5], however the A14 and/or A19 tyrosines are predominantly iodinated. A19 is an invariant residue in the insulin sequence [6] and is thought to be in an area important in maintaining the structural integrity necessary for insulin action.…”

mentioning

confidence: 99%

B1-3,5-diiodotyrosine insulin: A valid tracer for insulin

et al. 1977

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Insulin, specifically substituted at the PheB1 position with 3,5-diiodotyrosine, has been tested in several biological and immunological systems. Immunoreactivity was assessed using antisera specific for different parts of the insulin molecule. Biological activity in vitro was estimated on isolated rat fat cells. In vivo bioactivity (hypoglycaemia) and metabolism (metabolic and urinary clearance rates, half-life, apparent distribution space) were measured by infusion of the material into greyhounds. The results indicated that this B1-labelled insulin preparation was biologically fully active and, unlike randomly labelled preparations of iodoinsulin, was metabolised with kinetics indistinguishable from those of the unlabelled hormone. We suggest that this material is a valid tracer for insulin, fulfilling the criteria of high specific activity and biological identity to the native hormone.

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“…The removal of the Bpoc group from IVa was carried out as previously described^ 14 1. HBr · H--GlutOBuO-Asn-TyrOVCysOTrO-Asn-OBu' was coupled to Bpoc-Leu-Tyr(Bu r )-Gln-Leu-OH fl7 l by the DCC/HOBt methodl 13 !…”

Section: Bpoc-l Eu-tyr(bu ^-Gln-l Eu-glu(obu *)-A Sn--tyrfij-cysftrtjmentioning

confidence: 99%

The Synthesis of [A19-3-Iodotyrosine] and [A19-3,5-Diiodotyrosine]insulin (porcine)

Wieneke¹,

Danho²,

Büllesbach³

et al. 1983

Hoppe-Seyler´s Zeitschrift für physiologische Chemie

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The chemical synthesis of [Tyr(I) A19 ] and [Tyr(I 2 ) A19 ]insulin (porcine), using the amino-acid derivatives 3-iodotyrosine and 3,5-diiodotyrosine is described. The synthesis of the iodinated -chains were performed by segment condensation in solution using acid labile protecting groups. The hydroxyl groups of Tyr(I) and Tyr(l2) were unprotected. For the temporary protection of the -amino groups of the A-chain segments containing iodinated tyrosines, the 1 -(4-biphenylyl)-l -methylethoxycarbonyl group was selected. After deprotection and sulphitolysis the iodinated -chain tetra-S-sulphonates were purified by ion exchange chromatography on DEAE cellulose at pH 5.6. Reduction to the sulphhydryl form and the combination with native porcine B-chain yielded [Tyr(I) A19 ] and [Tyr(I 2 ) A19 ]insulin (porcine), respectively.Purification of the first product was achieved by gel filtration and of the later by ion exchange chromatography on CM-cellulose at pH 4.5 and gel filtration. The monoiodinated insulin had a biological activity of 24 ± 2% and the diiodinated analogue 2.6 ± 0.2% as determined in an in vitro lipogenesis assay with epidymal adipocytes. Synthesen von [A19-3-Iodtyrosin] und [A19-3,5-Diiodtyrosin]insulin (Schwein)Zusammenfassung: Die chemische Synthese von [Tyr(I) A19 ] und [Tyr(I 2 ) A19 ]Insulin (Schwein) wird beschrieben. Die Darstellung der [Tyr(I) A19 ]-A-Kette und der [Tyr(I 2 ) A19 ]-A-Kette erfolgte durch Segmentkondensation in Lösung unter Anwendung säurelabiler Schutzgruppen. Die Hydroxylfunktionen von 3-Iodtyrosin und 3,5-Diiodtyrosin blieben im Verlaufe der Synthese ungeschützt. Alle A-Kettenfragmente mit iodiertem Tyrosin wurden am N-Terminus durch die l -(4-Biphenylyl)-1 -methylethoxycarbonyl-Gruppe temporär geschützt. Nach der Deblockierung und der Sulfitolyse wurden die iodierten A-Kettentetra-iS-sulfonate durch lonenaustauschchroma-

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Iodination of insulin in aqueous and organic solvents

Cited by 30 publications

References 14 publications

The effect of iodination of particular tyrosine residues on the hormonal activity of insulin

The effect of iodination of particular tyrosine residues on the hormonal activity of insulin

B1-3,5-diiodotyrosine insulin: A valid tracer for insulin

The Synthesis of [A19-3-Iodotyrosine] and [A19-3,5-Diiodotyrosine]insulin (porcine)

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