Metallopeptide
Metallopeptides (also called metal-peptides or metal peptide complexes) are peptides that contain one or more metal ions in their structure. This specific type of peptide are, just like metalloproteins, metallofoldamers. And very similar to metalloproteins, metallopeptide's functionality is attibuted through the contained metal ion cofactor. These short structured peptides are often employed to develop mimics of metalloproteins and systems similar to artificial metalloenzymes.
A multitude of naturally occurring peptides display biological and chemical activities when bound to various metal ions. Where different metal ion cofactor can lead to different reactivity and even different folding and physical characteristics (e.g. solubility or stability) of the structure. Synthetic equivalents of such peptides are engineered to bind metal ions and display a variety of physical, chemical, and biological reactivity and characteristics.
Examples[edit]
In the last 40 years, there has been a significant amount of research on metal binding peptides and their characteristics, structures, and chemical reactivities.[1]
To name a few examples of ongoing research: Vincent L. Pecoraro and his group investigate the interaction of peptides with heavy metals in the body; Katherine Franz leads a group studying Cu-binding peptides; Angela Lombardi and her unit focus on the development of artificial metalloenzymes and similar peptide systems, and the group of Peter Faller focuses on redox reactivity of Cu-peptides.[2] [3]
Natural[edit]
Natural metallopeptides with antibiotic, antimicrobial and anticancer properties have been of particular interest to the scientific community (e.g. the divalent bacitracin, histatin and Fe/Cu-bleomycin).[4] [5] At the same time there is an increasing attention to the role of metalloppeptides in disease development. For example, metallochemical interactions in brain tissue can contribute to neurodegenerative conditions due to the naturally high concentration of metal ions in the brain. Hence the metallochemical reactions occurring outside the physiologically healthy concentrations, can contribute to the development of diseases such as Alzheimer's disease. The condition is related to the β-amyloid metallopeptides.[6] Another example are infectious prion polypeptides and specific isoforms of prion protein which contribute to disease transmission and development.[7]
Artificial[edit]
De novo designed peptides which self-assemble in the presence of Cu, forming supramolecular assemblies were presented by Korendovych et al.[8] Additionally there are examples of metallopeptides that are, at least partially, composed of non-natural amino acids with possible applications in drug discovery and biomaterials. [9]
Metal coordination[edit]
Being a type of molecules that are often only activated for biological and chemical function following metal-binding, the specific coordination of metal ions imposes certain restrictions and requirements onto metallopeptides. Usually metal cofactors are coordinated by nitrogen, oxygen or sulfur centers belonging to amino acid residues of the peptide. These donor groups can be introduced by histidine (or the corresponding imidazole), cysteine (thiolate group), as well as carboxylate substituents (e.g by aspartate) but are not limited to these. The other amino acid residues, including non-natural amino acids and the peptide backbone have been shown to bind metal centers and provide donor groups. The research on metal-binding of peptides ranges from coordination of biometals (such as Calcium, Magnesium, Manganese, Zinc, Sodium, Potassium, and Iron) to heavy metals (such as Arsenic, Mercury, and Cadmium). [10] [11]
Synthesis and analysis[edit]
Biosynthesis[edit]
Main article: Peptide biosynthesis
Peptides are synthesized in living organisms inside the cell analogously to proteins.
Chemical synthesis[edit]
Solid phase peptide synthesis (SPPS) is a well-established method for producing synthetic peptides. SPPS enables the building of a peptide chain by sequential interactions of amino acid derivatives.
Analysis[edit]
The interaction between metal ions and peptides are typically studied in solution using spectroscopic or electrochemical methods. Amongst which are circular dichroism (CD), nuclear magnetic resonance (NMR) spectroscopy, cyclic voltammetry, and mass spectrometry (MS).[1]
See also[edit]
References[edit]
- ^ a b Murariu M, Dragan ES, Drochioiu G (June 2010). "Model peptide-based system used for the investigation of metal ions binding to histidine-containing polypeptides". Biopolymers. 93 (6): 497–508. doi:10.1002/bip.21385. PMID 20091672.
- ^ DeGrado WF, Summa CM, Pavone V, Nastri F, Lombardi A (1999-06-07). "De novo design and structural characterization of proteins and metalloproteins". Annual Review of Biochemistry. 68 (1): 779–819. doi:10.1146/annurev.biochem.68.1.779. PMID 10872466.
- ^ Okafor M, Champomier O, Raibaut L, Ozkan S, El Kholti N, Ory S, et al. (2024-04-05). "Restoring cellular copper homeostasis in Alzheimer disease: a novel peptide shuttle is internalized by an ATP-dependent endocytosis pathway involving Rab5- and Rab14-endosomes". Frontiers in Molecular Biosciences. 11: 1355963. doi:10.3389/fmolb.2024.1355963. PMC 11026709. PMID 38645276.
- ^ Ming LJ (2010-09-25). "Metallopeptides — from Drug Discovery to Catalysis". Journal of the Chinese Chemical Society. 57 (3A): 285–299. doi:10.1002/jccs.201000043. ISSN 0009-4536.
- ^ Conklin SE, Bridgman EC, Su Q, Riggs-Gelasco P, Haas KL, Franz KJ (August 2017). "Specific Histidine Residues Confer Histatin Peptides with Copper-Dependent Activity against Candida albicans". Biochemistry. 56 (32): 4244–4255. doi:10.1021/acs.biochem.7b00348. PMC 5937946. PMID 28763199.
- ^ Barnham KJ, McKinstry WJ, Multhaup G, Galatis D, Morton CJ, Curtain CC, et al. (May 2003). "Structure of the Alzheimer's disease amyloid precursor protein copper binding domain. A regulator of neuronal copper homeostasis". The Journal of Biological Chemistry. 278 (19): 17401–17407. doi:10.1074/jbc.M300629200. PMID 12611883.
- ^ Daus ML (January 2016). "Disease Transmission by Misfolded Prion-Protein Isoforms, Prion-Like Amyloids, Functional Amyloids and the Central Dogma". Biology. 5 (1): 2. doi:10.3390/biology5010002. PMC 4810159. PMID 26742083.
- ^ Makhlynets OV, Gosavi PM, Korendovych IV (July 2016). "Short Self-Assembling Peptides Are Able to Bind to Copper and Activate Oxygen". Angewandte Chemie. 55 (31): 9017–9020. doi:10.1002/anie.201602480. PMC 5064842. PMID 27276534.
- ^ Lewis JC (April 2015). "Metallopeptide catalysts and artificial metalloenzymes containing unnatural amino acids". Current Opinion in Chemical Biology. Biocatalysis and biotransformation • Bioinorganic chemistry. 25: 27–35. doi:10.1016/j.cbpa.2014.12.016. PMC 4380757. PMID 25545848.
- ^ Rulísek L, Vondrásek J (September 1998). "Coordination geometries of selected transition metal ions (Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Hg2+) in metalloproteins". Journal of Inorganic Biochemistry. 71 (3–4): 115–127. doi:10.1016/S0162-0134(98)10042-9. PMID 9833317.
- ^ Hausinger RP (December 2019). "New metal cofactors and recent metallocofactor insights". Current Opinion in Structural Biology. Catalysis and Regulation ● Protein Nucleic Interactions. 59: 1–8. doi:10.1016/j.sbi.2018.12.008. PMID 30711735.