GIP (3-42), human

Product Name: GIP (3-42), human

Sequence One Letter Code: EGTFISDYSIAMDKIHQQDFVNWLLAQKGKKNDWKHNITQ

Sequence Three Letter Code: H-Glu-Gly-Thr-Phe-Ile-Ser-Asp-Tyr-Ser-Ile-Ala-Met-Asp-Lys-Ile-His-Gln-Gln-Asp-Phe-Val-Asn-Trp-Leu-Leu-Ala-Gln-Lys-Gly-Lys-Lys-Asn-Asp-Trp-Lys-His-Asn-Ile-Thr-Gln-OH

Cas No: 1802086-25-4

Chemical Formula:C214H324N58O63S

Molecular Weight: 4749.6

Purity: 95%

Form: Lyophilized

Storage Conditions: - 20 °C

Research Area: Diabetes and Metabolic Syndrome

SMILES: CC[C@H](C)[C@@H](C(=O)N[C@@H](CC1=CNC=N1)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC2=CC=CC=C2)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC3=CNC4=CC=CC=C43)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(=O)N)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H](CC(=O)O)C(=O)N[C@@H](CC5=CNC6=CC=CC=C65)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC7=CNC=N7)C(=O)N[C@@H](CC(=O)N)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCC(=O)N)C(=O)O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CCSC)NC(=O)[C@H](C)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H](CC8=CC=C(C=C8)O)NC(=O)[C@H](CC(=O)O)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CC9=CC=CC=C9)NC(=O)[C@H]([C@@H](C)O)NC(=O)CNC(=O)[C@H](CCC(=O)O)N

IUPAC: (4S)-4-amino-5-[[2-[[(2S,3R)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S,3S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-5-amino-1-[[(2S)-6-amino-1-[[2-[[(2S)-6-amino-1-[[(2S)-6-amino-1-[[(2S)-4-amino-1-[[(2S)-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-4-amino-1-[[(2S,3S)-1-[[(2S,3R)-1-[[(1S)-4-amino-1-carboxy-4-oxobutyl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-1-oxohexan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-1,4-dioxobutan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-3-(1H-imidazol-4-yl)-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-1-oxo-3-phenylpropan-2-yl]amino]-3-hydroxy-1-oxobutan-2-yl]amino]-2-oxoethyl]amino]-5-oxopentanoic acid

INCHIKEY: KYTGHAJCQXMQDP-YEJNUZODSA-N

INCHI:

InChI=1S/C214H324N58O63S/c1-20-107(11)171(271-206(326)155(101-274)264-191(311)140(82-117-57-59-122(277)60-58-117)250-200(320)153(93-169(295)296)260-205(325)154(100-273)265-210(330)173(109(13)22-3)269-203(323)142(81-116-46-28-25-29-47-116)261-212(332)175(113(17)275)266-164(286)99-232-179(299)125(220)61-70-165(287)288)208(328)237-112(16)178(298)240-136(71-77-336-19)187(307)258-150(90-166(289)290)198(318)244-132(56-38-43-76-219)188(308)268-172(108(12)21-2)209(329)262-146(86-121-97-229-103-235-121)194(314)246-134(63-67-157(222)279)185(305)245-135(64-68-158(223)280)186(306)257-151(91-167(291)292)199(319)251-141(80-115-44-26-24-27-45-115)202(322)267-170(106(9)10)207(327)263-148(88-161(226)283)197(317)252-144(84-119-95-231-127-51-33-31-49-124(119)127)193(313)249-139(79-105(7)8)190(310)248-138(78-104(5)6)189(309)236-111(15)177(297)239-133(62-66-156(221)278)184(304)241-128(52-34-39-72-215)180(300)233-98-163(285)238-129(53-35-40-73-216)181(301)242-130(54-36-41-74-217)183(303)255-147(87-160(225)282)196(316)259-152(92-168(293)294)201(321)253-143(83-118-94-230-126-50-32-30-48-123(118)126)192(312)243-131(55-37-42-75-218)182(302)254-145(85-120-96-228-102-234-120)195(315)256-149(89-162(227)284)204(324)270-174(110(14)23-4)211(331)272-176(114(18)276)213(333)247-137(214(334)335)65-69-159(224)281/h24-33,44-51,57-60,94-97,102-114,125,128-155,170-176,230-231,273-277H,20-23,34-43,52-56,61-93,98-101,215-220H2,1-19H3,(H2,221,278)(H2,222,279)(H2,223,280)(H2,224,281)(H2,225,282)(H2,226,283)(H2,227,284)(H,228,234)(H,229,235)(H,232,299)(H,233,300)(H,236,309)(H,237,328)(H,238,285)(H,239,297)(H,240,298)(H,241,304)(H,242,301)(H,243,312)(H,244,318)(H,245,305)(H,246,314)(H,247,333)(H,248,310)(H,249,313)(H,250,320)(H,251,319)(H,252,317)(H,253,321)(H,254,302)(H,255,303)(H,256,315)(H,257,306)(H,258,307)(H,259,316)(H,260,325)(H,261,332)(H,262,329)(H,263,327)(H,264,311)(H,265,330)(H,266,286)(H,267,322)(H,268,308)(H,269,323)(H,270,324)(H,271,326)(H,272,331)(H,287,288)(H,289,290)(H,291,292)(H,293,294)(H,295,296)(H,334,335)/t107-,108-,109-,110-,111-,112-,113+,114+,125-,128-,129-,130-,131-,132-,133-,134-,135-,136-,137-,138-,139-,140-,141-,142-,143-,144-,145-,146-,147-,148-,149-,150-,151-,152-,153-,154-,155-,170-,171-,172-,173-,174-,175-,176-/m0/s1

Source / Species: human

Conjugation: Unconjugated

Code Nacres: NA.26

Application: GIP (3–42) is a truncated form of human glucose-dependent insulinotropic polypeptide produced through dipeptidyl peptidase IV (DPP-IV)–mediated removal of the N-terminal dipeptide from full-length GIP. In contrast to intact GIP, which acts as an incretin hormone that stimulates insulin secretion, GIP (3–42) functions as a potent antagonist of the GIP receptor. This antagonistic activity makes the peptide a valuable tool for investigating incretin signaling and receptor modulation in metabolic research. GIP (3–42) is widely applied in studies of insulin secretion, glucose homeostasis, and metabolic regulation, as well as in investigations of the physiological consequences of DPP-IV–mediated incretin degradation. Its ability to selectively inhibit GIP receptor activity supports research exploring the roles of incretin pathways in diabetes, obesity, and metabolic disease mechanisms.

Current Research: Glucose-dependent insulinotropic polypeptide (GIP) is one of the primary incretin hormones involved in regulating glucose metabolism. Secreted by enteroendocrine K cells in the small intestine after nutrient intake, GIP enhances glucose-stimulated insulin secretion from pancreatic β-cells and contributes to maintaining postprandial glucose homeostasis. However, GIP signaling is tightly regulated in the body, and one important regulatory mechanism involves enzymatic cleavage by dipeptidyl peptidase IV (DPP-IV). One of the key products of this enzymatic process is GIP (3–42), a truncated peptide generated when the N-terminal dipeptide of the full-length hormone is removed. This structural modification significantly alters the biological activity of the peptide. Unlike intact GIP, which acts as an agonist at the GIP receptor, GIP (3–42) functions as a potent antagonist, making it an important experimental tool in metabolic and endocrine research. Formation Through DPP-IV–Mediated Cleavage Full-length human GIP consists of 42 amino acids and is rapidly processed in circulation by the enzyme DPP-IV, a serine protease widely expressed on endothelial cells and in plasma. DPP-IV cleaves peptides that contain proline or alanine residues at the second position, a structural feature present in GIP. Through this cleavage, the enzyme removes the first two amino acids from the N-terminus of GIP, producing GIP (3–42). This truncation disrupts the peptide’s ability to activate the GIP receptor (GIPR), a class B G protein–coupled receptor responsible for mediating incretin signaling. While the truncated peptide retains the ability to bind the receptor, it does not trigger the same intracellular signaling pathways, allowing it to function as a competitive antagonist. Antagonistic Activity at the GIP Receptor The biological importance of GIP (3–42) lies in its ability to inhibit GIP receptor signaling. In contrast to native GIP, which promotes insulin secretion and metabolic responses, the truncated peptide blocks receptor activation and prevents downstream signaling events. This antagonistic property allows researchers to selectively suppress GIP-mediated pathways in experimental systems. By comparing physiological responses in the presence or absence of GIP (3–42), scientists can investigate the specific contributions of GIP signaling to metabolic regulation. Experimental studies using GIP (3–42) have been used to evaluate: Insulin secretion dynamics in pancreatic β-cells Receptor binding interactions and ligand competition Intracellular signaling pathways triggered by GIPR activation Hormonal regulation of glucose metabolism Through these approaches, GIP (3–42) has become a valuable molecular probe for understanding the functional role of incretin hormones. Role in Studies of Glucose Homeostasis Incretin hormones such as GIP and GLP-1 play a critical role in coordinating glucose metabolism after food intake. GIP (3–42) provides researchers with a means of selectively blocking one branch of the incretin system, making it possible to analyze how GIP contributes to glucose homeostasis and insulin regulation. In laboratory models, GIP (3–42) has been applied in experiments examining: Glucose-stimulated insulin secretion Hormonal control of pancreatic β-cell function Interactions between GIP and other metabolic signaling pathways Effects of incretin signaling on nutrient metabolism These investigations are essential for clarifying how incretin hormones influence metabolic physiology and how disruptions in these pathways may contribute to metabolic disorders. Investigating DPP-IV–Mediated Incretin Degradation The formation of GIP (3–42) also highlights the broader importance of DPP-IV–mediated incretin degradation. DPP-IV rapidly inactivates incretin hormones in circulation, limiting their biological half-life. This enzymatic process plays a major role in regulating hormone activity and metabolic signaling. Because GIP (3–42) is a direct product of this cleavage reaction, it serves as a useful tool for studying the physiological consequences of incretin degradation. Research involving this peptide can help scientists examine: The balance between active and inactive incretin forms Mechanisms controlling incretin hormone stability Regulatory roles of DPP-IV in endocrine signaling Interactions between incretin hormones and metabolic enzymes These insights are particularly important in metabolic research, where DPP-IV inhibitors are widely studied for their effects on incretin activity. Applications in Metabolic Disease Research GIP receptor signaling has been implicated in several metabolic conditions, including diabetes, obesity, and metabolic syndrome. By acting as a selective antagonist, GIP (3–42) allows researchers to explore how modulation of this pathway influences metabolic outcomes. Experimental applications include studies focused on: Insulin secretion and pancreatic β-cell responsiveness Hormonal regulation of glucose metabolism Interactions between incretin signaling and adipose tissue function Mechanisms underlying metabolic disease development Through these investigations, GIP (3–42) contributes to a deeper understanding of how incretin pathways participate in systemic metabolic regulation. Conclusion GIP (3–42) is an important truncated peptide generated through DPP-IV–mediated cleavage of the incretin hormone GIP. Unlike the intact hormone, which stimulates insulin secretion through activation of the GIP receptor, GIP (3–42) acts as a potent receptor antagonist, selectively blocking GIP signaling. Because of this unique property, the peptide has become widely used in research focused on incretin biology, insulin secretion, and metabolic regulation. By enabling targeted inhibition of GIP receptor activity, GIP (3–42) continues to serve as a valuable experimental tool for investigating the complex mechanisms that govern glucose homeostasis and metabolic disease pathways.