Synthesis of potent agonists of Substance P by replacement of Met11 with Glu(OBzl) and N‐terminal glutamine with Glp of the C‐terminal hexapeptide and heptapeptide of Substance P

GEORGE STAVROPOULOS; KOSTAS KARAGIANNIS; STAVROS ANAGNOSTIDES; ITZHAK MINISTROUSKI; ZVI SELINGER; MICHAEL CHOREV

doi:10.1111/j.1399-3011.1995.tb01313.x

Synthesis of potent agonists of Substance P by replacement of Met¹¹ with Glu(OBzl) and N‐terminal glutamine with Glp of the C‐terminal hexapeptide and heptapeptide of Substance P

GEORGE STAVROPOULOS^*
, KOSTAS KARAGIANNIS
, STAVROS ANAGNOSTIDES
, ITZHAK MINISTROUSKI
, ZVI SELINGER
, MICHAEL CHOREV

^*Corresponding author for this work

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

The analogues [Glp⁶,Glu(OBzl)¹¹]SP_6‐11 and [Glp⁵,Glu(OBzl)¹¹]SP_5‐11) of the C‐terminal hexapeptide and heptapeptide of Substance P have been synthesized by conventional solution methods. In each analogue the N‐terminal glutamine has been replaced by pyroglutamic acid, while the COOCH₂C₆H₅ ester group has replaced the SCH₃ group of the Met¹¹ side chain. The in vitro activity of both analogues has been determined on three biological preparations: guinea pig ileum (GPI), rat vas deferens (RVD) and rat portal vein (RPV). The results showed that both analogues are highly potent and selective agonists on GPI through the NK‐1 receptor. They are more potent than SP itself, with 1.54 and 1.25 respective values of relative potency on GPI. Their selectivity has been studied by utilizing atropine‐treated guinea pig ileum (GPI + At). The analogues showed low activity on RVD and RPV tissues, which represent NK‐2 and NK‐3 monoreceptor assay, respectively. © Munksgaard 1995.

Original language	English
Pages (from-to)	508-513
Number of pages	6
Journal	International Journal of Peptide and Protein Research
Volume	45
Issue number	6
DOIs	https://doi.org/10.1111/j.1399-3011.1995.tb01313.x
State	Published - Jun 1995

Keywords

NK‐1 receptor
Substance P C‐terminal analogues
Substance P agonist
glutamine replacement
guinea pig ileum
methionine replacement

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10.1111/j.1399-3011.1995.tb01313.x

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STAVROPOULOS, GEORGE., KARAGIANNIS, KOSTAS., ANAGNOSTIDES, STAVROS., MINISTROUSKI, ITZHAK., SELINGER, ZVI., & CHOREV, MICHAEL. (1995). Synthesis of potent agonists of Substance P by replacement of Met¹¹ with Glu(OBzl) and N‐terminal glutamine with Glp of the C‐terminal hexapeptide and heptapeptide of Substance P. International Journal of Peptide and Protein Research, 45(6), 508-513. https://doi.org/10.1111/j.1399-3011.1995.tb01313.x

@article{ff36e675cc4b453b848c9b9f86781d37,

title = "Synthesis of potent agonists of Substance P by replacement of Met11 with Glu(OBzl) and N‐terminal glutamine with Glp of the C‐terminal hexapeptide and heptapeptide of Substance P",

abstract = "The analogues [Glp6,Glu(OBzl)11]SP6‐11 and [Glp5,Glu(OBzl)11]SP5‐11) of the C‐terminal hexapeptide and heptapeptide of Substance P have been synthesized by conventional solution methods. In each analogue the N‐terminal glutamine has been replaced by pyroglutamic acid, while the COOCH2C6H5 ester group has replaced the SCH3 group of the Met11 side chain. The in vitro activity of both analogues has been determined on three biological preparations: guinea pig ileum (GPI), rat vas deferens (RVD) and rat portal vein (RPV). The results showed that both analogues are highly potent and selective agonists on GPI through the NK‐1 receptor. They are more potent than SP itself, with 1.54 and 1.25 respective values of relative potency on GPI. Their selectivity has been studied by utilizing atropine‐treated guinea pig ileum (GPI + At). The analogues showed low activity on RVD and RPV tissues, which represent NK‐2 and NK‐3 monoreceptor assay, respectively. {\textcopyright} Munksgaard 1995.",

keywords = "NK‐1 receptor, Substance P C‐terminal analogues, Substance P agonist, glutamine replacement, guinea pig ileum, methionine replacement",

author = "GEORGE STAVROPOULOS and KOSTAS KARAGIANNIS and STAVROS ANAGNOSTIDES and ITZHAK MINISTROUSKI and ZVI SELINGER and MICHAEL CHOREV",

year = "1995",

month = jun,

doi = "10.1111/j.1399-3011.1995.tb01313.x",

language = "אנגלית",

volume = "45",

pages = "508--513",

journal = "International Journal of Peptide and Protein Research",

issn = "0367-8377",

publisher = "Wiley-Blackwell Publishing Ltd",

number = "6",

}

STAVROPOULOS, GEORGE, KARAGIANNIS, KOSTAS, ANAGNOSTIDES, STAVROS, MINISTROUSKI, ITZHAK, SELINGER, ZVI & CHOREV, MICHAEL 1995, 'Synthesis of potent agonists of Substance P by replacement of Met¹¹ with Glu(OBzl) and N‐terminal glutamine with Glp of the C‐terminal hexapeptide and heptapeptide of Substance P', International Journal of Peptide and Protein Research, vol. 45, no. 6, pp. 508-513. https://doi.org/10.1111/j.1399-3011.1995.tb01313.x

Synthesis of potent agonists of Substance P by replacement of Met¹¹ with Glu(OBzl) and N‐terminal glutamine with Glp of the C‐terminal hexapeptide and heptapeptide of Substance P. / STAVROPOULOS, GEORGE; KARAGIANNIS, KOSTAS; ANAGNOSTIDES, STAVROS et al.
In: International Journal of Peptide and Protein Research, Vol. 45, No. 6, 06.1995, p. 508-513.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Synthesis of potent agonists of Substance P by replacement of Met11 with Glu(OBzl) and N‐terminal glutamine with Glp of the C‐terminal hexapeptide and heptapeptide of Substance P

AU - STAVROPOULOS, GEORGE

AU - KARAGIANNIS, KOSTAS

AU - ANAGNOSTIDES, STAVROS

AU - MINISTROUSKI, ITZHAK

AU - SELINGER, ZVI

AU - CHOREV, MICHAEL

PY - 1995/6

Y1 - 1995/6

N2 - The analogues [Glp6,Glu(OBzl)11]SP6‐11 and [Glp5,Glu(OBzl)11]SP5‐11) of the C‐terminal hexapeptide and heptapeptide of Substance P have been synthesized by conventional solution methods. In each analogue the N‐terminal glutamine has been replaced by pyroglutamic acid, while the COOCH2C6H5 ester group has replaced the SCH3 group of the Met11 side chain. The in vitro activity of both analogues has been determined on three biological preparations: guinea pig ileum (GPI), rat vas deferens (RVD) and rat portal vein (RPV). The results showed that both analogues are highly potent and selective agonists on GPI through the NK‐1 receptor. They are more potent than SP itself, with 1.54 and 1.25 respective values of relative potency on GPI. Their selectivity has been studied by utilizing atropine‐treated guinea pig ileum (GPI + At). The analogues showed low activity on RVD and RPV tissues, which represent NK‐2 and NK‐3 monoreceptor assay, respectively. © Munksgaard 1995.

AB - The analogues [Glp6,Glu(OBzl)11]SP6‐11 and [Glp5,Glu(OBzl)11]SP5‐11) of the C‐terminal hexapeptide and heptapeptide of Substance P have been synthesized by conventional solution methods. In each analogue the N‐terminal glutamine has been replaced by pyroglutamic acid, while the COOCH2C6H5 ester group has replaced the SCH3 group of the Met11 side chain. The in vitro activity of both analogues has been determined on three biological preparations: guinea pig ileum (GPI), rat vas deferens (RVD) and rat portal vein (RPV). The results showed that both analogues are highly potent and selective agonists on GPI through the NK‐1 receptor. They are more potent than SP itself, with 1.54 and 1.25 respective values of relative potency on GPI. Their selectivity has been studied by utilizing atropine‐treated guinea pig ileum (GPI + At). The analogues showed low activity on RVD and RPV tissues, which represent NK‐2 and NK‐3 monoreceptor assay, respectively. © Munksgaard 1995.

KW - NK‐1 receptor

KW - Substance P C‐terminal analogues

KW - Substance P agonist

KW - glutamine replacement

KW - guinea pig ileum

KW - methionine replacement

UR - https://www.scopus.com/pages/publications/0029016784

U2 - 10.1111/j.1399-3011.1995.tb01313.x

DO - 10.1111/j.1399-3011.1995.tb01313.x

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C2 - 7558580

AN - SCOPUS:0029016784

SN - 0367-8377

VL - 45

SP - 508

EP - 513

JO - International Journal of Peptide and Protein Research

JF - International Journal of Peptide and Protein Research

IS - 6

ER -

STAVROPOULOS GEORGE, KARAGIANNIS KOSTAS, ANAGNOSTIDES STAVROS, MINISTROUSKI ITZHAK, SELINGER ZVI, CHOREV MICHAEL. Synthesis of potent agonists of Substance P by replacement of Met¹¹ with Glu(OBzl) and N‐terminal glutamine with Glp of the C‐terminal hexapeptide and heptapeptide of Substance P. International Journal of Peptide and Protein Research. 1995 Jun;45(6):508-513. doi: 10.1111/j.1399-3011.1995.tb01313.x

Synthesis of potent agonists of Substance P by replacement of Met¹¹ with Glu(OBzl) and N‐terminal glutamine with Glp of the C‐terminal hexapeptide and heptapeptide of Substance P

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Keywords

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