Gly-His-Thr-Asp-Amide, an Insulin-Activating Peptide from the Human Pancreas Is a Strong Cu(II) but a Weak Zn(II) Chelator
Abstract
The Cu(II) and Zn(II) binding abilities of Gly-His-Thr-Asp-amide (GHTD-am), a tetrapeptide coreleased from the pancreas along with insulin, were studied using UV–vis and circular dichroism spectroscopies, potentiometry, and calorimetry. GHTD-am is a very strong Cu(II) chelator, forming a three-nitrogen complex with a conditional affinity constant C K at pH 7.4 of 4.5 × 10 12 M –1 . The fourth coordination site can be occupied by a solvent molecule or a ternary ligand, such as imidazole, with C K on the order of several hundred reciprocal molar. The Zn(II) binding ability of GHTD-am is relatively weak, with C K values at pH 7.4 of 3.0 × 10 4 and 2.0 × 10 3 M –1 for the first and second GHTD-am molecule coordinated, respectively. These results are discussed in light of the modes of interactions of Zn(II) and Cu(II) ions with insulin. A direct effect of GHTD-am on the Zn(II) interactions with insulin is unlikely, but its Cu(II) complex may have a biological relevance because of its high affinity and ability to form ternary complexes.
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The first additional deprotonation probably corresponds to a water molecule (pK = 9.61) within the equatorial plane of the Cu(GHK) species.
“The first probably corresponds to a water molecule (pK = 9.61) within the equatorial plane of the Cu(GHK) species [20,21].”
From Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate (2020) · cites this paper as [21]
The assignment of the deprotonation to a water molecule instead of an imidazole N1 from another Cu(GHK) complex is rationalized by the lack of drastic changes of CD parameters expected upon formation of imidazole-bridged dimeric or tetrameric species.
“The aforementioned assignment of the deprotonation to a water molecule instead of an imidazole N1 from another Cu(GHK) complex (with concomitant polynuclear species formation) is rationalized by the lack of drastic changes of CD parameters that would be expected upon formation of imidazole-bridged dimeric or tetrameric species [21,22,23].”
From Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate (2020) · cites this paper as [21]
Urocanic acid contains an imidazole ring that could form a stable ternary Cu(II) complex with GHK in a manner similar to other Xaa-His peptides.
“Urocanic acid, a by-product of L-histidine, contains an imidazole ring that could form a stable ternary Cu(II) complex with GHK in a manner similar to other Xaa-His peptides such as Trp–His–Trp–Ser–Lys–Asn–Arg, Gly–His–Thr–Asp, and Ala–His–His [20,21,34].”
From Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate (2020) · cites this paper as [21]
The cK7.4 for Cu(GHK)(Im) is comparable to values previously reported for the Xaa-His peptides Trp-His-Trp-Ser-Lys-Asn-Arg (1022 ± 70 M−1) and Gly-His-Thr-Asp (440 ± 14 M−1).
“Global fitting of all spectroscopic data yielded a value of cK7.4 = 725 ± 22 M−1 (Figure 3D,E) for Cu(GHK)(Im), which is comparable to the values previously reported for the Xaa-His peptides Trp–His–Trp–Ser–Lys–Asn–Arg (1022 ± 70 M−1) and Gly–His–Thr–Asp (440 ± 14 M−1) [20,21].”
From Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate (2020) · cites this paper as [21]
GHK coordinates copper via a tridentate nitrogenous chelate, with the fourth binding site open to coordination by an external ligand.
“As mentioned above, GHK coordinates copper via a tridentate nitrogenous chelate, with the fourth binding site, being open to coordination by an external ligand.”
From Ternary Cu(II) Complex with GHK Peptide and Cis-Urocanic Acid as a Potential Physiologically Functional Copper Chelate (2020) · cites this paper as [21]
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Self-citationReactive oxygen generation by minimal copper binding peptide motifsPreprint
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- Authors
- Kotuniak, R., Fra̧czyk, T., Skrobecki, P., Płonka, D., & Bal, W.
- Affiliations
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences (PL)
- Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Pawińskiego 5a, 02-106 Warsaw, Poland
- Corresponding author
- Bal, Wojciech
- Venue
- Inorganic Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-11-27
- Volume
- 57
- Issue
- 24
- Pages
- 15507-15516
- ISSN
- 0020-1669 (ISSN-L)
- 1520-510X
- OpenAlex
- W2903478605
- Cited by
- 15
- References
- 54
- Citations by year
- 2025: 1 · 2024: 2 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 2
- FWCI
- 1.04
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Inorganic Chemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Narodowe Centrum Nauki (2016/23/B/ST5/02253)
- Topics
- Health Sciences › Medicine › Oncology › Metal complexes synthesis and properties
- Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
- Physical Sciences › Chemistry › Organic Chemistry › Inorganic and Organometallic Chemistry
- Keywords
- tetrapeptide, copper(II) chelation, metal binding affinity, ternary metal complexes, imidazole, pancreatic peptides
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