Structure-Activity Relationships of Glucose-Dependent Insulinotropic Polypeptide (GIP)

Six GIP1-30NH2 analogs were synthesized with modifications (de-protonation, N-methylation, reversed chirality, and substitution) at positions 1, 3, and 4 of the N-terminus, and additionally, a cyclized GIP derivative was synthesized. The relationship between altered structure to biological activity...

Full description

Saved in:
Bibliographic Details
Published inBiological chemistry Vol. 384; no. 3; pp. 403 - 407
Main Authors Hinke, S.A., Gelling, R., Manhart, S., Lynn, F., Pederson, R.A., Kühn-Wache, K., Rosche, F., Demuth, H.-U., Coy, D., McIntosh, C.H.S.
Format Journal Article
LanguageEnglish
Published Germany Walter de Gruyter 01.03.2003
Subjects
Adenylyl Cyclases - metabolism
Animals
Binding, Competitive
CHO Cells
Cricetinae
Cyclic AMP - biosynthesis
Enzyme Activation
Gastric Inhibitory Polypeptide - chemistry
Gastric Inhibitory Polypeptide - metabolism
Gastric Inhibitory Polypeptide - pharmacology
Glucose - metabolism
Insulin - metabolism
Insulin Secretion
Peptide Fragments - chemistry
Peptide Fragments - metabolism
Peptide Fragments - pharmacology
Structure-Activity Relationship
Online AccessGet full text
ISSN1431-6730
DOI10.1515/BC.2003.046

Cover

Abstract Six GIP1-30NH2 analogs were synthesized with modifications (de-protonation, N-methylation, reversed chirality, and substitution) at positions 1, 3, and 4 of the N-terminus, and additionally, a cyclized GIP derivative was synthesized. The relationship between altered structure to biological activity was assessed by measuring receptor binding affinity and ability to stimulate adenylyl cyclase in CHO-K1 cells transfected with the wild-type GIP receptor (wtGIPR). These structureactivity relationship studies demonstrate the importance of the GIP N-terminus and highlight structural constraints that can be introduced in GIP analogs. These analogs may be useful starting points for design of peptides with enhanced in vivo bioactivity.
AbstractList Six GIP(1-NH2) analogs were synthesized with modifications (de-protonation, N-methylation, reversed chirality, and substitution) at positions 1, 3, and 4 of the N-terminus, and additionally, a cyclized GIP derivative was synthesized. The relationship between altered structure to biological activity was assessed by measuring receptor binding affinity and ability to stimulate adenylyl cyclase in CHO-K1 cells transfected with the wild-type GIP receptor (wtGIPR). These structure-activity relationship studies demonstrate the importance of the GIP N-terminus and highlight structural constraints that can be introduced in GIP analogs. These analogs may be useful starting points for design of peptides with enhanced in vivo bioactivity.Six GIP(1-NH2) analogs were synthesized with modifications (de-protonation, N-methylation, reversed chirality, and substitution) at positions 1, 3, and 4 of the N-terminus, and additionally, a cyclized GIP derivative was synthesized. The relationship between altered structure to biological activity was assessed by measuring receptor binding affinity and ability to stimulate adenylyl cyclase in CHO-K1 cells transfected with the wild-type GIP receptor (wtGIPR). These structure-activity relationship studies demonstrate the importance of the GIP N-terminus and highlight structural constraints that can be introduced in GIP analogs. These analogs may be useful starting points for design of peptides with enhanced in vivo bioactivity.
Six GIP1-30NH2 analogs were synthesized with modifications (de-protonation, N-methylation, reversed chirality, and substitution) at positions 1, 3, and 4 of the N-terminus, and additionally, a cyclized GIP derivative was synthesized. The relationship between altered structure to biological activity was assessed by measuring receptor binding affinity and ability to stimulate adenylyl cyclase in CHO-K1 cells transfected with the wild-type GIP receptor (wtGIPR). These structureactivity relationship studies demonstrate the importance of the GIP N-terminus and highlight structural constraints that can be introduced in GIP analogs. These analogs may be useful starting points for design of peptides with enhanced in vivo bioactivity.
Six GIP(1-NH2) analogs were synthesized with modifications (de-protonation, N-methylation, reversed chirality, and substitution) at positions 1, 3, and 4 of the N-terminus, and additionally, a cyclized GIP derivative was synthesized. The relationship between altered structure to biological activity was assessed by measuring receptor binding affinity and ability to stimulate adenylyl cyclase in CHO-K1 cells transfected with the wild-type GIP receptor (wtGIPR). These structure-activity relationship studies demonstrate the importance of the GIP N-terminus and highlight structural constraints that can be introduced in GIP analogs. These analogs may be useful starting points for design of peptides with enhanced in vivo bioactivity.
Author Kühn-Wache, K.
Coy, D.
Pederson, R.A.
Demuth, H.-U.
Hinke, S.A.
Rosche, F.
Lynn, F.
McIntosh, C.H.S.
Gelling, R.
Manhart, S.
Author_xml – sequence: 1
  givenname: S.A.
  surname: Hinke
  fullname: Hinke, S.A.
– sequence: 2
  givenname: R.
  surname: Gelling
  fullname: Gelling, R.
– sequence: 3
  givenname: S.
  surname: Manhart
  fullname: Manhart, S.
– sequence: 4
  givenname: F.
  surname: Lynn
  fullname: Lynn, F.
– sequence: 5
  givenname: R.A.
  surname: Pederson
  fullname: Pederson, R.A.
– sequence: 6
  givenname: K.
  surname: Kühn-Wache
  fullname: Kühn-Wache, K.
– sequence: 7
  givenname: F.
  surname: Rosche
  fullname: Rosche, F.
– sequence: 8
  givenname: H.-U.
  surname: Demuth
  fullname: Demuth, H.-U.
– sequence: 9
  givenname: D.
  surname: Coy
  fullname: Coy, D.
– sequence: 10
  givenname: C.H.S.
  surname: McIntosh
  fullname: McIntosh, C.H.S.
BackLink https://www.ncbi.nlm.nih.gov/pubmed/12715891$$D View this record in MEDLINE/PubMed
BookMark eNptkT1PwzAURT0U0Q-Y2FEmBEIpduzE6dgUKBUVFKgYWKzUeRGGNA62g-i_J6WlA2J6y7lXuud1UavUJSB0RHCfhCS8SEb9AGPaxyxqoQ5hlPgRp7iNuta-YYxjzOg-apOAkzAekA56fnKmlq424A-lU5_KrbxHKFKndGlfVWU9nXvjopbagn8JFZQZlM6blLYuVKmd0ZWS3kwXqwoqpzLwTseT2dkB2svTwsLh9vbQ_PpqPrrxp_fjyWg49SUNqPPzMM1lyBlIKRcQM8A4JwxTSXCcZYxGmEeSpxldxGwQBZHEOR1ABDxuRgWE9tDJprYy-qMG68RSWQlFkZagays4DYKYRmvweAvWiyVkojJqmZqV-BXRAGQDSKOtNZALqdyPBWdSVQiCxVqwSEZiLVg0gpvM-Z_MrvZf2t_Qyjr42qGpeRfNi3goHuZMhHT6Qu5uE5HQb44Ki_c
CitedBy_id crossref_primary_10_1124_mol_109_060111
crossref_primary_10_1111_j_1463_1326_2004_00455_x
crossref_primary_10_1016_S0006_291X_03_01361_5
crossref_primary_10_1530_JME_13_0137
crossref_primary_10_1016_j_abb_2007_03_001
crossref_primary_10_1016_j_npep_2003_09_002
crossref_primary_10_1016_j_ejphar_2014_08_019
crossref_primary_10_1016_j_molmet_2025_102118
crossref_primary_10_1021_acs_jmedchem_4c00111
crossref_primary_10_1074_jbc_RA120_016334
crossref_primary_10_1016_j_bcp_2012_04_015
crossref_primary_10_1074_jbc_M111_276808
crossref_primary_10_1016_j_lfs_2004_03_024
crossref_primary_10_1124_jpet_106_107011
Cites_doi 10.1016/0196-9781(95)00090-7
10.1172/JCI119060
10.1677/joe.0.1650639
10.1016/0196-9781(94)90206-2
10.1210/er.16.3.390
10.1006/bbrc.2002.6364
10.1210/er.20.6.876
10.1038/nm727
10.1111/j.1399-3011.1998.tb00664.x
10.1016/0303-7207(95)03701-2
10.1111/j.1432-1033.1993.tb17986.x
10.1016/S0167-4838(01)00181-9
10.1016/0167-4838(83)90261-3
10.2174/092986730611220401163238
10.2337/diabetes.51.3.652
10.2337/diabetes.50.5.1004
10.1016/S0167-0115(97)00009-8
10.1074/jbc.271.38.23222
10.2337/diabetes.47.8.1253
10.1210/en.136.8.3585
10.1016/S0026-0495(99)90090-2
10.1021/jm010091q
10.1007/s001250050779
10.1021/bi001527r
10.1007/0-306-46826-3_21
ContentType Journal Article
DBID BSCLL
AAYXX
CITATION
CGR
CUY
CVF
ECM
EIF
NPM
7X8
DOI 10.1515/BC.2003.046
DatabaseName Istex
CrossRef
Medline
MEDLINE
MEDLINE (Ovid)
MEDLINE
MEDLINE
PubMed
MEDLINE - Academic
DatabaseTitle CrossRef
MEDLINE
Medline Complete
MEDLINE with Full Text
PubMed
MEDLINE (Ovid)
MEDLINE - Academic
DatabaseTitleList MEDLINE - Academic

MEDLINE
Database_xml – sequence: 1
  dbid: NPM
  name: PubMed
  url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed
  sourceTypes: Index Database
– sequence: 2
  dbid: EIF
  name: MEDLINE
  url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search
  sourceTypes: Index Database
DeliveryMethod fulltext_linktorsrc
Discipline Anatomy & Physiology
Chemistry
Biology
EndPage 407
ExternalDocumentID 12715891
10_1515_BC_2003_046
ark_67375_QT4_53LZ1NKB_B
Genre Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S
Journal Article
GrantInformation_xml – fundername: NIDDK NIH HHS
  grantid: DK-18370
GroupedDBID ---
-~0
-~X
.GJ
0R~
0~D
23N
34G
36B
4.4
53G
5GY
5RE
9-L
AAAEU
AAFPC
AAGVJ
AAKRG
AALGR
AAONY
AAOWA
AAPJK
AAQCX
AASQH
AASQN
AAWFC
AAXCG
AAXMT
ABABW
ABAOT
ABAQN
ABCQX
ABFKT
ABIQR
ABJNI
ABLVI
ABMIY
ABPLS
ABRDF
ABRQL
ABTAH
ABUVI
ABVMU
ABWLS
ABXMZ
ABYBW
ACEFL
ACGFS
ACIWK
ACMKP
ACPMA
ACPRK
ACXLN
ACZBO
ADALX
ADEQT
ADGQD
ADGYE
ADOZN
ADUQZ
AEGVQ
AEICA
AEJTT
AEKEB
AENEX
AEQDQ
AERZL
AEXIE
AFAUI
AFBAA
AFCXV
AFFNX
AFGNR
AFQUK
AFRAH
AFYRI
AGBEV
AGGNV
AGWTP
AHVWV
AHXUK
AI.
AIERV
AIKXB
AJATJ
AJPIC
AKXKS
ALMA_UNASSIGNED_HOLDINGS
AMAVY
ASPBG
ASYPN
AVWKF
AZFZN
AZMOX
BAKPI
BBCWN
BBDJO
BCIFA
BDLBQ
BSCLL
CAG
COF
CS3
DA2
DBYYV
DU5
EBS
EJD
EMOBN
F5P
FEDTE
FSTRU
HVGLF
HZ~
IL9
IY9
KDIRW
L7B
O9-
OBS
OES
OHH
OVD
QD8
RDG
SA.
SLJYH
TEORI
UK5
VH1
WH7
WTRAM
ZY4
~KM
~Z8
AAYXX
ABDRH
ACDEB
ACRPL
ACUND
ACYCL
ADNMO
AECWL
AFBDD
AFSHE
AGQPQ
AHGSO
AIWOI
CITATION
LVMAB
.55
354
3O-
AAFNC
AAOTM
ABUBZ
CGR
CUY
CVF
ECM
EIF
NPM
X7M
ZXP
7X8
ADNPR
DSRVY
ID FETCH-LOGICAL-c323t-f5afc574ecccbe84e00f1403c108dd436076c7ad3b849626c0f39e6e78730213
ISSN 1431-6730
IngestDate Thu Sep 04 21:33:40 EDT 2025
Wed Feb 19 02:33:27 EST 2025
Thu Apr 24 23:10:28 EDT 2025
Tue Jul 01 01:07:15 EDT 2025
Wed Oct 30 09:18:44 EDT 2024
IsPeerReviewed true
IsScholarly true
Issue 3
Language English
LinkModel OpenURL
MergedId FETCHMERGED-LOGICAL-c323t-f5afc574ecccbe84e00f1403c108dd436076c7ad3b849626c0f39e6e78730213
Notes bc.2003.046.pdf
istex:8BDBC9561AFDB14A7DFD24577E553951B1F7F3CF
ArticleID:bchm.384.3.403
ark:/67375/QT4-53LZ1NKB-B
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
PMID 12715891
PQID 73228361
PQPubID 23479
PageCount 5
ParticipantIDs proquest_miscellaneous_73228361
pubmed_primary_12715891
crossref_citationtrail_10_1515_BC_2003_046
crossref_primary_10_1515_BC_2003_046
istex_primary_ark_67375_QT4_53LZ1NKB_B
ProviderPackageCode CITATION
AAYXX
PublicationCentury 2000
PublicationDate 2003-03-01
PublicationDateYYYYMMDD 2003-03-01
PublicationDate_xml – month: 03
  year: 2003
  text: 2003-03-01
  day: 01
PublicationDecade 2000
PublicationPlace Germany
PublicationPlace_xml – name: Germany
PublicationTitle Biological chemistry
PublicationTitleAlternate Biological Chemistry
PublicationYear 2003
Publisher Walter de Gruyter
Publisher_xml – name: Walter de Gruyter
References p_27
p_28
p_23
p_24
p_26
Hinke S.A. (p_9) 2001; 1547
Holst J.J. (p_11) 1999; 6
p_20
p_21
p_16
p_17
p_2
p_1
p_19
p_4
p_3
p_13
p_14
p_5
p_15
p_8
p_7
Parker J.C. (p_22) 1998; 52
Fischer G. (p_6) 1983; 742
p_10
Holst J.J. (p_12) 2001; 234
References_xml – ident: p_4
  doi: 10.1016/0196-9781(95)00090-7
– ident: p_27
  doi: 10.1172/JCI119060
– ident: p_21
  doi: 10.1677/joe.0.1650639
– ident: p_3
  doi: 10.1016/0196-9781(94)90206-2
– ident: p_5
  doi: 10.1210/er.16.3.390
– ident: p_7
  doi: 10.1006/bbrc.2002.6364
– ident: p_14
  doi: 10.1210/er.20.6.876
– ident: p_20
  doi: 10.1038/nm727
– volume: 52
  start-page: 398
  year: 1998
  ident: p_22
  publication-title: J. Peptide Res.
  doi: 10.1111/j.1399-3011.1998.tb00664.x
– ident: p_28
  doi: 10.1016/0303-7207(95)03701-2
– ident: p_19
  doi: 10.1111/j.1432-1033.1993.tb17986.x
– volume: 1547
  start-page: 143
  year: 2001
  ident: p_9
  publication-title: Biochim. Biophys. Acta
  doi: 10.1016/S0167-4838(01)00181-9
– volume: 742
  start-page: 452
  year: 1983
  ident: p_6
  publication-title: Biochim. Biophys. Acta
  doi: 10.1016/0167-4838(83)90261-3
– volume: 6
  start-page: 1005
  year: 1999
  ident: p_11
  publication-title: Curr. Med. Chem.
  doi: 10.2174/092986730611220401163238
– ident: p_10
  doi: 10.2337/diabetes.51.3.652
– ident: p_17
  doi: 10.2337/diabetes.50.5.1004
– ident: p_8
  doi: 10.1016/S0167-0115(97)00009-8
– volume: 234
  start-page: 75
  year: 2001
  ident: p_12
  publication-title: Scand. J. Clin. Lab. Invest. (Suppl.)
– ident: p_24
  doi: 10.1074/jbc.271.38.23222
– ident: p_26
  doi: 10.2337/diabetes.47.8.1253
– ident: p_15
  doi: 10.1210/en.136.8.3585
– ident: p_23
  doi: 10.1016/S0026-0495(99)90090-2
– ident: p_1
  doi: 10.1021/jm010091q
– ident: p_13
  doi: 10.1007/s001250050779
– ident: p_2
  doi: 10.1021/bi001527r
– ident: p_16
  doi: 10.1007/0-306-46826-3_21
SSID ssj0008043
Score 1.7959821
SecondaryResourceType review_article
Snippet Six GIP1-30NH2 analogs were synthesized with modifications (de-protonation, N-methylation, reversed chirality, and substitution) at positions 1, 3, and 4 of...
Six GIP(1-NH2) analogs were synthesized with modifications (de-protonation, N-methylation, reversed chirality, and substitution) at positions 1, 3, and 4 of...
SourceID proquest
pubmed
crossref
istex
SourceType Aggregation Database
Index Database
Enrichment Source
Publisher
StartPage 403
SubjectTerms Adenylyl Cyclases - metabolism
Animals
Binding, Competitive
CHO Cells
Cricetinae
Cyclic AMP - biosynthesis
Enzyme Activation
Gastric Inhibitory Polypeptide - chemistry
Gastric Inhibitory Polypeptide - metabolism
Gastric Inhibitory Polypeptide - pharmacology
Glucose - metabolism
Insulin - metabolism
Insulin Secretion
Peptide Fragments - chemistry
Peptide Fragments - metabolism
Peptide Fragments - pharmacology
Structure-Activity Relationship
Title Structure-Activity Relationships of Glucose-Dependent Insulinotropic Polypeptide (GIP)
URI https://api.istex.fr/ark:/67375/QT4-53LZ1NKB-B/fulltext.pdf
https://www.ncbi.nlm.nih.gov/pubmed/12715891
https://www.proquest.com/docview/73228361
Volume 384
hasFullText 1
inHoldings 1
isFullTextHit
isPrint
link http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV3db9MwELegFYIXBBsf5TMP0wRIGU5tJ-ljU3Ud0BUQ2VTxYiWOo1VAUpVMYvz1nB07adUiPl4iK3KcyL_L-c6--x1CB7mgsA6FqcuEx1ya-9QdYCrcjKaw2IciTTV35-nMPzmjb-dsbmu1m-ySKj0SP3fmlfwPqnAPcFVZsv-AbDMo3IA24AtXQBiuf4XxJ03-ermSrkpP0FUgVja47WKx1FEaJibdtdVuKxt-XlarcrkQqkwD-KKgOTJtbk7efLC7A_asd9EoSGHLw7U71oWJ7gHMi3ZjdCI117dJ3W-ygU6T4iKpk4R0OFB7pj-9ag1psdjcjCBtNJbRn2CPqGwCvK5gSV0EzkgSWVOXVPMbbKtxphkvopHmaz3CdAdZ9uw9Pz6bTnk8nsfXUbcPXgLuoO5wEo3Pm6U4xHWGhf0qk6AJw79eG3zDJOmqv-vH7_0NbXfEd9Bt4zA4wxr9u-iaLPbQ_rBIqvLblXPo6BBefTayh25EtnVzZJHaR-fbYuJsiIlT5s6WmDibYuKsiYnzAoTk5T0UH4_j0Ylrymm4gvRJ5eYsyQULKPy0IpUhlRjniq1ReDjMMkp8HPgiSDKShnQAfq7AORlIX4JKJ2AJkvuoU5SFfIgcNkjBCmaE5X4CBiCsUyKgIfMVUdKAJLiHXtkJ5cJQzauKJ1-5cjlh9nk0UvVPCYfZ76GDpvOyZljZ3e1QI9P0SVZfVFBiwPjHmHJGpp-92buIRz303ELHYaLV-VdSyPLyOw-I4nryvR56UCPavq8feKq85qM_PvsY3Wrl_gnqAIDyKZilVfrMCN8vpnuOGw
linkProvider Walter de Gruyter
openUrl ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Structure-activity+relationships+of+glucose-dependent+insulinotropic+polypeptide+%28GIP%29&rft.jtitle=Biological+chemistry&rft.au=Hinke%2C+Simon+A&rft.au=Gelling%2C+Rick&rft.au=Manhart%2C+Susanne&rft.au=Lynn%2C+Francis&rft.date=2003-03-01&rft.issn=1431-6730&rft.volume=384&rft.issue=3&rft.spage=403&rft_id=info:doi/10.1515%2FBC.2003.046&rft.externalDBID=NO_FULL_TEXT
thumbnail_l http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/lc.gif&issn=1431-6730&client=summon
thumbnail_m http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/mc.gif&issn=1431-6730&client=summon
thumbnail_s http://covers-cdn.summon.serialssolutions.com/index.aspx?isbn=/sc.gif&issn=1431-6730&client=summon