Synthesis of the Merrifield Resin Esters of N-Protected Amino Acids With the Aid of Hydrogen Bonding1

Horiki, Kusuo; Igano, Ken'ichi; Inouye, Ken

doi:10.1246/cl.1978.165

Cited by 58 publications

(28 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The peptides Leu-Tyr-Ala-Ser-Ser-AsnPro-Glu-Tyr-Leu-Ser-Ala-Ser-Asp-Val-Phe (P4) and GlyLys-Lys-Asn-Gly-Arg-Ile-Leu-Thr-Leu-Pro-Arg-Ser-AsnPro-Ser (P5), corresponding to residues 952-967 and 1328-1343, respectively, of the insulin proreceptor sequence (18), were synthesized with an additional cysteine residue at their carboxyl termini. The Merrifield resin ester of Nprotected cysteine was prepared by esterification of chloromethylated, 1% crosslinked, styrene-divinylbenzene copolymer with the cysteine derivative in the presence of KF in anhydrous dimethylformamide as described by Horiki et al (26). The extent of amino acid substitution on the resin was 0.25 mmol/g.…”

mentioning

confidence: 99%

An antipeptide antibody that specifically inhibits insulin receptor autophosphorylation and protein kinase activity.

Herrera

Petruzzelli

Thomas

et al. 1985

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

View full text Add to dashboard Cite

Two site-specific antibodies that immunoprecipitate the human insulin receptor have been prepared by immunizing rabbits with chemically synthesized peptides derived from the cDNA-predicted amino acid sequence of the (B subunit of the proreceptor. Antibodies to the carboxyl terminus (AbP5) and to a domain around tyrosine-960 (AbP4) specifically recognize the (3 subunit of the receptor on inmunoblots.Both antibodies immunoprecipitated 12'I-labeled insulin-receptor complexes and the autophosphorylated receptor. Although neither antibody inhibited insulin binding to the receptor, both insulin-dependent autophosphorylation and exogenous substrate phosphorylation were inhibited by AbP4. Inhibition by AbP4 was dependent upon the phosphorylation state of the receptor; it was not detected when the receptor was autophosphorylated prior to addition of AbP4. AbP4 did not inhibit activity of the related epidermal growth factor (EGF)-receptor tyrosine protein kinase nor did it inhibit the activity of cAMP-dependent kinase or protein kinase C. The observation that an antibody directed to residues 952-967 of the proreceptor neutralizes the protein kinase activity of the (3 subunit suggests that this region may play a critical role in the function of the hormone-dependent, protein tyrosine-specific kinase activity of the insulin receptor.The mature insulin receptor, an integral membrane glycoprotein, is a tetramer (Mr 350,000-400,000) composed of two a subunits (Mr 135,000) and two , ( subunits (Mr 95,000) linked by disulfide bonds (1-4). The a subunit binds insulin (3-6). This interaction stimulates the phosphorylation of the ,B subunit on tyrosine, threonine, and serine residues, in intact cells (7), and on tyrosine residues, in cell-free preparations of receptor (8-15). The insulin-dependent protein tyrosine kinase also catalyzes the phosphorylation of tyrosine residues in exogenous proteins and peptides (8,(14)(15)(16)(17). The kinase activity is intrinsic to the insulin receptor, as first shown by its copurification to homogeneity with insulinbinding activity (12,13,16) and then confirmed when the homology between the deduced amino acid sequence of the

show abstract

mentioning

confidence: 99%

An antipeptide antibody that specifically inhibits insulin receptor autophosphorylation and protein kinase activity.

Herrera

Petruzzelli

Thomas

et al. 1985

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

View full text Add to dashboard Cite

show abstract

“…The Boc-Cys(Mob)-CM resin with a capacity of 0.3-0.5 mequiv/g was obtained according to published procedures (Mob ) 4-methoxybenzyl). 58 All of the N R -tert-butoxycarbonyl (BOC) protected amino acids with side chain protection were purchased from Bachem Inc. 60 were synthesized in our laboratory (Z ) benzyloxycarbonyl, Bzl ) benzyl, Bzl(3Br) ) 3-bromobenzyl, Z(2Br) ) 2-bromobenzyloxycarbonyl, Z(2Cl) ) 2-chlorobenzyloxycarbonyl. Fmoc--Ala and Fmoc-Gaba were the products of Chem-Impex Intl.…”

Section: Methodsmentioning

confidence: 99%

Somatostatin Receptor 1 Selective Analogues: 3. Dicyclic Peptides

et al. 2004

View full text Add to dashboard Cite

The binding affinity of short chain somatostatin (SRIF) analogues at the five human SRIF receptors (sst) was determined to identify sterically constrained somatostatin receptor subtype 1 (sst(1)) selective scaffolds. Des-AA(1,2,4,13)-[d-Trp(8)]SRIF (2) retained high binding affinity at all receptors but sst(1), Des-AA(1,2,4,5)-[d-Trp(8)]SRIF (3) at sst(4) and sst(5), and Des-AA(1,2,4,5,13)-[d-Trp(8)]SRIF (4) at sst(2) and sst(4) (AA = amino acid). Des-AA(1,2,4,12,13)-[d-Trp(8)]SRIF (6) was potent and sst(4)-selective (>25-fold); Des-AA(1,2,5,12,13)-[d-Trp(8)]SRIF (7) and Des-AA(1,2,4,5,12,13)-[d-Trp(8)]-SRIF (9, ODT-8) were most potent at sst(4) and moderately potent at all other receptors. Dicyclic SRIF agonists of the sst(1)-selective Des-AA(1,5)-[Tyr(2),d-Trp(8),IAmp(9)]SRIF, (14, sst(1) IC(50) = 14 nM) were prepared in which a lactam bridge introduced additional conformational constraint (IAmp = 4-(N-isopropyl)-aminomethylphenylalanine). Cyclo(7-12)Des-AA(1,5)-[Tyr(2),Glu(7),d-Trp(8),IAmp(9),hhLys(12)]SRIF (31) (sst(1) IC(50) = 16 nM) and cyclo(7-12) Des-AA(1,2,5)-[Glu(7),d-Trp(8),IAmp(9),m-I-Tyr(11),hhLys(12)]SRIF (45) (sst(1) IC(50) = 6.1 nM) had equal or improved affinities over that of the parent 14. Binding affinity was decreased in all other cases with alternate bridging constraints such as cyclo (6-11), cyclo (6-12), and cyclo (7-11). Compound 45 is an agonist (EC(50) = 8.8 nM) in the adenylate cyclase assay.

show abstract

“…In the case of immobilization onto Merrifield-type resins [Merrifield, Paramax, polyethylene glycol (PEG) (4) and PEG (16)] the KF or Cs 2 CO 3 method [22,23] was applied. Dimethylamino sensor molecules and substance 6a were attached starting from cesium carboxylates, because no reaction was observed with KF as base.…”

Section: Attachment To Solid Supportmentioning

confidence: 99%

Gel‐Phase ¹³C NMR Spectroscopy of Selected Solid Phase Systems

Braunshier

Hametner

2007

QSAR Comb. Sci.

View full text Add to dashboard Cite

Studies on the applicability of conventional liquid-state NMR spectroscopy for the analysis of solid-phase organic reactions directly on the resin will be described. For a systematic investigation small and easily assignable molecules substituted with a chain of varying length were synthesized. In a subsequent step these so-called sensor molecules were attached to commercially available resins. After swelling experiments, 13 C NMR spectra of the solid phase systems in gel form were recorded using Composite Pulse Decoupling (CPD) and Attached Proton Test (APT) techniques. The quality of the resulting spectra was analyzed using the half-height linewidths of the signals as the most important criterion. Based on these data, the parameters to obtain high quality spectra were determined.

show abstract

Synthesis of the Merrifield Resin Esters of N-Protected Amino Acids With the Aid of Hydrogen Bonding1

Cited by 58 publications

References 8 publications

An antipeptide antibody that specifically inhibits insulin receptor autophosphorylation and protein kinase activity.

An antipeptide antibody that specifically inhibits insulin receptor autophosphorylation and protein kinase activity.

Somatostatin Receptor 1 Selective Analogues: 3. Dicyclic Peptides

Gel‐Phase ¹³C NMR Spectroscopy of Selected Solid Phase Systems

Contact Info

Product

Resources

About

Synthesis of the Merrifield Resin Esters of N-Protected Amino Acids With the Aid of Hydrogen Bonding1

Cited by 58 publications

References 8 publications

An antipeptide antibody that specifically inhibits insulin receptor autophosphorylation and protein kinase activity.

An antipeptide antibody that specifically inhibits insulin receptor autophosphorylation and protein kinase activity.

Somatostatin Receptor 1 Selective Analogues: 3. Dicyclic Peptides

Gel‐Phase 13C NMR Spectroscopy of Selected Solid Phase Systems

Contact Info

Product

Resources

About

Gel‐Phase ¹³C NMR Spectroscopy of Selected Solid Phase Systems