O-Benzotriazolyl-N,N,N′,N′-tetramethyluronium Hexafluorophosphate as Coupling Reagent for the Synthesis of Peptides of Biological Interest

Dourtoglou, Vassilis; Gross, Bernard; Lambropoulou, Vassiliki; Zioudrou, Christine

doi:10.1055/s-1984-30895

Cited by 301 publications

(180 citation statements)

References 0 publications

Supporting

Mentioning

167

Contrasting

Unclassified

Order By: Relevance

“…For that purpose, we first combined mutations at positions 11 and 28 which individually resulted in a decreased affinity for VPAC 2 receptor without any change in the affinity for VPAC 1 receptor. The [Ala 11,28 ]VIP analog clearly discriminated between VPAC 1 and VPAC 2 receptors (Tables I and II). Indeed, this VIP analog had the same affinity as native VIP for VPAC 1 receptor whereas it displayed a 44-fold lower affinity than native VIP for VPAC 2 receptor (Fig.…”

Section: Alanine Scanning Analysis Of Vip For Interacting With Human mentioning

confidence: 99%

“…7). The [Ala 11,28 ]VIP analog was as potent as native VIP for stimulating enzyme activity via VPAC 1 receptor whereas it was 21-fold less potent than VIP for stimulating enzyme activity via VPAC 2 receptor (Fig. 7).…”

Section: Alanine Scanning Analysis Of Vip For Interacting With Human mentioning

confidence: 99%

“…Since we also noted that position 22 in VIP was important for discriminating between VPAC 1 and VPAC 2 receptors with respect to adenylyl cyclase activation (see above), we further synthesized a VIP analog which combines 3 mutations at positions 11, 22, and 28. Quite interestingly, the [Ala 11,22,28 ]VIP analog was highly selective for VPAC 1 receptor. Indeed, its binding affinity for VPAC 2 receptor and subsequent biological potency in stimulating adenylyl cyclase were decreased by Ͼ1,000-fold as compared with native VIP (Fig.…”

Section: Alanine Scanning Analysis Of Vip For Interacting With Human mentioning

confidence: 99%

“…The interaction of the analogs with human VPAC 2 receptor is similar to that observed with VPAC 1 receptor, with three remarkable exceptions: substitution of Thr 11 and Asn 28 by alanine increased K i for binding to VPAC 2 receptor; substitution of Tyr 22 by alanine increased EC 50 for stimulating adenylyl cyclase activity through interaction with the VPAC 2 receptor. By combining 3 mutations at positions 11, 22, and 28, we developed the [Ala 11,22,28 ]VIP analog which constitutes the first highly selective (>1,000-fold) human VPAC 1 receptor agonist derived from VIP ever described.…”

mentioning

confidence: 99%

See 3 more Smart Citations

Identification of Key Residues for Interaction of Vasoactive Intestinal Peptide with Human VPAC1 and VPAC2Receptors and Development of a Highly Selective VPAC1Receptor Agonist

Nicole

Lins

Rouyer‐Fessard

et al. 2000

Journal of Biological Chemistry

158

159

View full text Add to dashboard Cite

The widespread neuropeptide vasoactive intestinal peptide (VIP) has two receptors VPAC 1 and VPAC 2 . Solid-phase syntheses of VIP analogs in which each amino acid has been changed to alanine (Ala scan) or glycine was achieved and each analog was tested for: (i) threedimensional structure by ab initio molecular modeling; (ii) ability to inhibit 125 ]VIP analog which constitutes the first highly selective (>1,000-fold) human VPAC 1 receptor agonist derived from VIP ever described. The vasoactive intestinal peptide (VIP)1 is a prominent neuropeptide with wide distribution in both peripheral and central nervous systems and a large spectrum of biological actions in mammals (1, 2). VIP-containing nerves and VIP effects have been described in digestive tract, cardiovascular system, airways, reproductive system, immune system, endocrine glands, and brain (1). Besides its short-term actions on exocrine secretions, hormone release, muscle relaxation, and metabolism (1, 2), VIP has been also characterized as a growth regulator for fetuses and tumor cells and during embryonic brain development (3). There are recent evidences for an important role of VIP in the perception of pain (4) and suppression of inflammation (5). Finally, VIP has been involved in diseases such as the watery diarrhea syndrome and clinical applications of VIP have been already suggested in impotence, asthma, lung injury, a variety of tumors and neurodegenerative diseases (1-3).VIP belongs to a large family of structurally related peptides (2, 6, 7) that comprises VIP, pituitary adenylate cyclase-activating peptide PACAP-27, and its C-terminal extended form PACAP-38, secretin, glucagon, and glucagon-like peptides-1 and -2, gastric inhibitory polypeptide, peptide histidine methionine amide, growth hormone-releasing factor (GRF), and peptides isolated from the venom of the Gila Monster. VIP and PACAP are the most closely related peptides in terms of structure and function (2, 6). They share two common receptors, VPAC 1 and VPAC 2 , which display high affinity for both VIP and PACAP (2,8). These receptors together with receptors for VIP-related peptides (see above) clearly constitute an original subfamily within the superfamily of G protein-coupled receptors (2, 9, 10). This subfamily referred to as class II (2) also comprises receptors for parathyroid hormone, calcitonin, corticotropin-releasing factor, and the so called EGF-TM7 receptors (11). Class II family of receptors for peptides display several common properties including large N-terminal extracellular domains containing highly conserved cystein residues, N-terminal leader sequences, and complex gene organization with many introns (2).Although the structure-function relationship of VIP receptors, including VPAC 1 and VPAC 2 , has been recently documented (2,9,(12)(13)(14)(15)(16)(17)(18)(19)(20), the structure-function relationship of VIP itself is still poorly understood. Some old studies carried out before the characterization and cloning of VIP receptor subtypes (21-23) indicated that: (i) th...

show abstract

Section: Alanine Scanning Analysis Of Vip For Interacting With Human mentioning

confidence: 99%

Section: Alanine Scanning Analysis Of Vip For Interacting With Human mentioning

confidence: 99%

Section: Alanine Scanning Analysis Of Vip For Interacting With Human mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Identification of Key Residues for Interaction of Vasoactive Intestinal Peptide with Human VPAC1 and VPAC2Receptors and Development of a Highly Selective VPAC1Receptor Agonist

Nicole

Lins

Rouyer‐Fessard

et al. 2000

Journal of Biological Chemistry

158

159

View full text Add to dashboard Cite

show abstract

“…Preventing the loss of configuration is one of the major challenges in peptide synthesis. [4][5][6][7][8] The activation of carboxylic acids using phosphonium 9-13) and uranium salts [14][15][16][17] is a fast, reliable process. These salts are prepared from a phosphonium or uronium cation bonded generally to a XO-group, normally a hydroxylamine derivative.…”

mentioning

confidence: 99%

Sulfonate Esters of 1-Hydroxypyridin-2(1H)-one and Ethyl 2-Cyano-2-(hydroxyimino)acetate (Oxyma) as Effective Peptide Coupling Reagents to Replace 1-Hydroxybenzotriazole and 1-Hydroxy-7-azabenzotriazole

Khattab

2010

Chem. Pharm. Bull.

View full text Add to dashboard Cite

The activation of carboxylic acids for the formation of amides or esters is an important process usually carried out using the so-called peptide coupling reagents. 1-3) This is followed by the reaction with the amine moiety of another amino acid to produce the desired peptide. The effective formation of a peptide bond not only depends on the reaction rate and yield but also on the suppression of the undesired racemization and other side reactions and thus minimizes the loss of the optical integrity at the chiral center of the carboxylic component. Preventing the loss of configuration is one of the major challenges in peptide synthesis. [4][5][6][7][8] The activation of carboxylic acids using phosphonium 9-13) and uranium salts [14][15][16][17] is a fast, reliable process. These salts are prepared from a phosphonium or uronium cation bonded generally to a XO-group, normally a hydroxylamine derivative. These salts combine the functions of activating agents with suppressing additives and were successfully introduced in peptide synthesis. 18) A common method of minimizing the loss of configuration during stepwise coupling in solution phase is to add an additive such as 1-hydroxy-benzotriazole (HOBt) to the coupling mixture. 19) Recently, 1-hydroxy-7-azabenzotriazole (HOAt) and its derived phophonium or uronium/guanidinuim salts have been described as favorable coupling additives or reagents for both solution 20) and solidphase synthesis. 21) HOAt has been reported to be more efficient than HOBt because of an anchimeric assistance effect caused by the pyridine ring. 22,23) These compounds enhance coupling yields and reduce the loss of chiral integrity during stepwise coupling.Esters of sulfonic acids and HOBt have been used for peptide coupling. [24][25][26][27][28] The reactivity of these sulfonate esters was shown to be directly related to the presence of electronwithdrawing substituents in both the HOBt and the sulfonic acid moieties. [29][30][31][32][33][34] This methodology has few applications, as the coupling process depends on the basicity and reactivity of the amino component. The use of such sulfonate esters for in situ coupling was often accompanied by the formation of a sulfonamide byproduct. 24,30) Such byproduct formation can be avoided by preactivation of the reactive carboxylic acid component.On the other hand, the use of a preactivation step is counterproductive, since the loss of configuration at the C-terminal carboxylic acid residue directly increases with preactivation time. 35) The replacement of HOBt by HOAt was expected to reduce the extent of configurational loss, but, on the contrary, the advantages of HOAt were lost during long preactivation times. 33,34) Oxyma (ethyl 2-cyano-2-(hydroxyimino)acetate) 4 has been tested as an additive for use in the carbodiimide approach for the formation of peptide bonds. It showed better performance than the classical HOBt and HOAt, which have recently been reported to exhibit explosive properties. Oxyma displayed a remarkable capacity to inhibit racemizati...

show abstract

¹⁴ C‐labelling of ipamorelin, a growth hormone secretagogue

Müller

Madsen

Foged

1998

J Label Compd Radiopharm

View full text Add to dashboard Cite

show abstract

O-Benzotriazolyl-N,N,N′,N′-tetramethyluronium Hexafluorophosphate as Coupling Reagent for the Synthesis of Peptides of Biological Interest

Cited by 301 publications

References 0 publications

Identification of Key Residues for Interaction of Vasoactive Intestinal Peptide with Human VPAC1 and VPAC2Receptors and Development of a Highly Selective VPAC1Receptor Agonist

Identification of Key Residues for Interaction of Vasoactive Intestinal Peptide with Human VPAC1 and VPAC2Receptors and Development of a Highly Selective VPAC1Receptor Agonist

Sulfonate Esters of 1-Hydroxypyridin-2(1H)-one and Ethyl 2-Cyano-2-(hydroxyimino)acetate (Oxyma) as Effective Peptide Coupling Reagents to Replace 1-Hydroxybenzotriazole and 1-Hydroxy-7-azabenzotriazole

¹⁴ C‐labelling of ipamorelin, a growth hormone secretagogue

Contact Info

Product

Resources

About

O-Benzotriazolyl-N,N,N′,N′-tetramethyluronium Hexafluorophosphate as Coupling Reagent for the Synthesis of Peptides of Biological Interest

Cited by 301 publications

References 0 publications

Identification of Key Residues for Interaction of Vasoactive Intestinal Peptide with Human VPAC1 and VPAC2Receptors and Development of a Highly Selective VPAC1Receptor Agonist

Identification of Key Residues for Interaction of Vasoactive Intestinal Peptide with Human VPAC1 and VPAC2Receptors and Development of a Highly Selective VPAC1Receptor Agonist

Sulfonate Esters of 1-Hydroxypyridin-2(1H)-one and Ethyl 2-Cyano-2-(hydroxyimino)acetate (Oxyma) as Effective Peptide Coupling Reagents to Replace 1-Hydroxybenzotriazole and 1-Hydroxy-7-azabenzotriazole

14 C‐labelling of ipamorelin, a growth hormone secretagogue

Contact Info

Product

Resources

About

¹⁴ C‐labelling of ipamorelin, a growth hormone secretagogue