Metal complexes of synthetic cyclic peptides

Gahan, Lawrence R.; Cusack, Rodney M.

doi:10.1016/j.poly.2018.06.030

Cited by 13 publications

(14 citation statements)

References 238 publications

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“…The shape of the patellamide macrocycle with eight nitrogen donors, the observation of a 10 4 fold increase of copper(II) concentration in ascidians (see above), and some early observations of metal ion coordination to patellamide derivatives has sparked the interest of coordination and bioinorganic chemists in naturally occurring patellamides. This involves unravelling their synthesis and in particular the solution and structural chemistry of patellamide complexes, primarily with copper(II), as well as in the reactivity of these patellamide complexes [23,25,46,60,77,86,87,[92][93][94].…”

Section: Structural Properties Of Patellamide Complexesmentioning

confidence: 99%

“…Therefore, it remains possible that patellamides might ultimately not provide any functional advantage to the host. Keeping this in mind, there are two important facts: (i) the copper concentration in ascidians is high (10 4 times higher than in the sea water and relatively high compared to other biologically relevant metal ions) [23,25,78,93,125], and (ii) the patellamide macrocycles are abundant in ascidians (see above) [28,29]. Copper thus appears important for the ascidian-Prochloron symbiosis, and it is likely that patellamide macrocycles play a major role for the activity revealed by copper.…”

Section: Possible Functions Of Patellamides In the Ascidian-prochloro...mentioning

confidence: 99%

“…Prochloron is able to synthesize various cyanobactins, which exhibit strong bioactivity and have been intensively studied with respect to their structural chemistry, catalytic properties and pharmacological application [22][23][24][25][26]. Here we focus on patellamides, which were discovered in 1981 by researchers in search of bioactive molecules for medical applications.…”

Section: Introduction Discovery Of Prochloron and The Ascidian-prochl...mentioning

confidence: 99%

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Possible Functional Roles of Patellamides in the Ascidian-Prochloron Symbiosis

et al. 2022

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Patellamides are highly bioactive compounds found along with other cyanobactins in the symbiosis between didemnid ascidians and the enigmatic cyanobacterium Prochloron. The biosynthetic pathway of patellamide synthesis is well understood, the relevant operons have been identified in the Prochloron genome and genes involved in patellamide synthesis are among the most highly transcribed cyanobacterial genes in hospite. However, a more detailed study of the in vivo dynamics of patellamides and their function in the ascidian-Prochloron symbiosis is complicated by the fact that Prochloron remains uncultivated despite numerous attempts since its discovery in 1975. A major challenge is to account for the highly dynamic microenvironmental conditions experienced by Prochloron in hospite, where light-dark cycles drive rapid shifts between hyperoxia and anoxia as well as pH variations from pH ~6 to ~10. Recently, work on patellamide analogues has pointed out a range of different catalytic functions of patellamide that could prove essential for the ascidian-Prochloron symbiosis and could be modulated by the strong microenvironmental dynamics. Here, we review fundamental properties of patellamides and their occurrence and dynamics in vitro and in vivo. We discuss possible functions of patellamides in the ascidian-Prochloron symbiosis and identify important knowledge gaps and needs for further experimental studies.

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Section: Structural Properties Of Patellamide Complexesmentioning

confidence: 99%

Section: Possible Functions Of Patellamides In the Ascidian-prochloro...mentioning

confidence: 99%

Section: Introduction Discovery Of Prochloron and The Ascidian-prochl...mentioning

confidence: 99%

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Possible Functional Roles of Patellamides in the Ascidian-Prochloron Symbiosis

et al. 2022

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“…These common amino acids form the spatial structure that mediates binding to metal ions. Moreover, many metal-binding peptides are now known, and their binding properties and structural positions in relation to metals are being studied [ 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Peptides can be highly selective and effective signaling molecules that bind to specific cell surface receptors, such as cancer cell receptors or ion channels, and exhibit various activities in cells [ 25 ].…”

Section: Introductionmentioning

confidence: 99%

Development of Cobalt-Binding Peptide Chelate from Human Serum Albumin: Cobalt-Binding Properties and Stability

Cho

Mirzapour‐Kouhdasht

Yun

et al. 2022

IJMS

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Radioactive isotopes are used as drugs or contrast agents in the medical field after being conjugated with chelates such as DOTA, NOTA, DTPA, TETA, CyDTA, TRITA, and DPDP. The N-terminal sequence of human serum albumin (HSA) is known as a metal binding site, such as for Co2+, Cu2+, and Ni2+. For this study, we designed and synthesized wAlb12 peptide from the N-terminal region of HSA, which can bind to cobalt, to develop a peptide-based chelate. The wAlb12 with a random coil structure tightly binds to the Co(II) ion. Moreover, the binding property of wAlb12 toward Co(II) was confirmed using various spectroscopic experiments. To identify the binding site of wAlb12, the analogs were synthesized by alanine scanning mutagenesis. Among them, H3A and Ac-wAlb12 did not bind to Co(II). The analysis of the binding regions confirmed that the His3 and α-amino group of the N-terminal region are important for Co(II) binding. The wAlb12 bound to Co(II) with Kd of 75 μM determined by isothermal titration calorimetry when analyzed by a single-site binding model. For the use of wAlb12 as a chelate in humans, its cytotoxicity and stability were investigated. Trypsin stability showed that the wAlb12 − Co(II) complex was more stable than wAlb12 alone. Furthermore, the cell viability analysis showed wAlb12 and wAlb12 + Co(II) to be non-toxic to the Raw 264.7 and HEK 293T cell lines. Therefore, a hot radioactive isotope such as cobalt-57 will have the same effect as a stable isotope cobalt. Accordingly, we expect wAlb12 to be used as a peptide chelate that binds with radioactive isotopes.

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“…Studies on unusual (or non-native) amino acid residues can further deepen our insight in the understanding native structure of peptides, predict it and/or design peptides with specific characteristics. Of special interest are azole-based peptides, due to their unique conformation and high propensity to metal complexation such as copper, calcium, or silver (Bertram and Pattenden 2007 ; Cusack et al 2002 ; Gahan and Cusack 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Thiazole–amino acids: influence of thiazole ring on conformational properties of amino acid residues

2021

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Post-translational modified thiazole–amino acid (Xaa–Tzl) residues have been found in macrocyclic peptides (e.g., thiopeptides and cyanobactins), which mostly inhibit protein synthesis in Gram + bacteria. Conformational study of the series of model compounds containing this structural motif with alanine, dehydroalanine, dehydrobutyrine and dehydrophenylalanine were performed using DFT method in various environments. The solid-state crystal structure conformations of thiazole–amino acid residues retrieved from the Cambridge Structural Database were also analysed. The studied structural units tend to adopt the unique semi-extended β2 conformation; which is stabilised mainly by N–H⋯NTzl hydrogen bond, and for dehydroamino acids also by π-electron conjugation. The conformational preferences of amino acids with a thiazole ring were compared with oxazole analogues and the role of the sulfur atom in stabilising the conformations of studied peptides was discussed.

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Metal complexes of synthetic cyclic peptides

Cited by 13 publications

References 238 publications

Possible Functional Roles of Patellamides in the Ascidian-Prochloron Symbiosis

Possible Functional Roles of Patellamides in the Ascidian-Prochloron Symbiosis

Development of Cobalt-Binding Peptide Chelate from Human Serum Albumin: Cobalt-Binding Properties and Stability

Thiazole–amino acids: influence of thiazole ring on conformational properties of amino acid residues

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