Stereochemistry of α‐aminoisobutyric acid peptides in solution: Helical conformations of protected decapeptides with repeating Aib‐<scp>L</scp>‐Ala and Aib‐<scp>L</scp>‐Val sequences

Vijayakumar, E. K. S.; Balaram, Padmanabhan

doi:10.1002/bip.360220911

Cited by 50 publications

(5 citation statements)

References 30 publications

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“…The measurements of the temperature dependences of chemical shifts (Δδ/ΔT) in hydrogen bonding solvents enable differentiation of the solvent-exposed and solvent-shielded peptide NH groups [39,40,41,42,43,44,45]. Since DMSO causes rapid decomposition of ferrocene peptides, their temperature dependences were determined in CDCl 3 solution [22,46,47].…”

Section: Resultsmentioning

confidence: 99%

Conjugates of 1'-Aminoferrocene-1-carboxylic Acid and Proline: Synthesis, Conformational Analysis and Biological Evaluation

et al. 2014

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Abstract:Our previous studies showed that alteration of dipeptides Y-Fca-Ala-OMe (III) into Y-Ala-Fca-OMe (IV) (Y = Ac, Boc; Fca = 1'-aminoferrocene-1-carboxylic acid) significantly influenced their conformational space. The novel bioconjugates Y-Fca-Pro-OMe (1, Y = Ac; 2, Y = Boc) and Y-Pro-Fca-OMe (3, Y = Boc; 4, Y = Ac) have been prepared in order to investigate the influence of proline, a well-known turn-inducer, on the conformational properties of small organometallic peptides with an exchanged constituent amino acid sequences. For this purpose, peptides 1-4 were subjected to detailed spectroscopic analysis (IR, NMR, CD spectroscopy) in solution. The conformation of peptide 3 in the solid state was determined. Furthermore, the ability of the prepared conjugates to inhibit the growth of estrogen receptor-responsive MCF-7 mammary carcinoma cells and HeLa cervical carcinoma cells was tested.

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Section: Resultsmentioning

confidence: 99%

Conjugates of 1'-Aminoferrocene-1-carboxylic Acid and Proline: Synthesis, Conformational Analysis and Biological Evaluation

et al. 2014

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“…The low Δδ/Δ T values (−2.4 ± 0.5 ppb K –1 ) correspond to either shielded protons which were initially downfield shifted or protons exposed to CDCl 3 and are therefore not informative in defining the hydrogen-bonding pattern. In contrast, the larger Δδ/Δ T values always reflect NH protons that were initially shielded from the solvent but are exposed during the unfolding of the IHB pattern or the dissociation of intermolecular aggregates upon heating. − ,− Here, the larger temperature coefficients observed for NH Fn and NH Ala of peptide 11 and NH Fn of peptide 7 , whose IR frequencies were concentration-dependent, provide additional confirmation of their aggregation tendency, while the case of the concentration-independent NH Ala of peptide 10 reflects its involvement in IHB-mediated folding. This is in good agreement with the results of the computational study where heterochiral derivatives 6 and 10 have both NH donors involved in hydrogen bonding.…”

Section: Resultsmentioning

confidence: 95%

Hydrogen Bond Patterning and Biological Activity of Ferrocene Conjugates with Homo- and Heterochiral Ala–Pro Dipeptides

Kovačević,

Čakić Semenčić,

Bagović

et al. 2024

Organometallics

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The chirality of the protein backbone influences both self-assembly and biological activity. In ferrocene-containing peptides, the sequence and chirality of the constitutive amino acids as well as the structure of the ferrocene scaffold strongly influence the conformational properties, whereas the biological activity is more strongly influenced by lipophilicity. A joint spectroscopic and computational study has shown that a relatively simple structural modification, such as changing the order of two amino acids in the dipeptide sequence from Pro−Ala (III) to Ala−Pro (IV), also alters the hydrogen bonding patterns from a mostly ten-membered (β-turn) to a seven-membered ring (γturn), which affects the antiproliferative activity of the ferrocene peptidomimetics studied. A systematic approach presented in this study allowed us to highlight the relevant structural variations that could lead to increased biological activity in similar ferrocenebased bioconjugates.

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“…While low ∆δ/∆T values (−2.4 ± 0.5 ppb K −1 ) correspond to either shielded protons which were initially downfield shifted, or protons exposed to CDCl 3 , larger ∆δ/∆T values always reflect initially shielded NH protons exposed during unfolding of intramolecularly hydrogen-bonded structures or dissociation of aggregates upon heating. [13,14,[35][36][37][38][39][40][41][42][43] Since the concentration-independent IR and NMR spectra excluded the self-assembly, the observed larger temperature coefficients are an additional confirmation of the intramolecularly folded conformations in peptides 2-5.…”

Section: Nmr Spectroscopymentioning

confidence: 90%

Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala Motifs

Kovačević

Semenčić

Radošević

et al. 2021

IJMS

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The concept of peptidomimetics is based on structural modifications of natural peptides that aim not only to mimic their 3D shape and biological function, but also to reduce their limitations. The peptidomimetic approach is used in medicinal chemistry to develop drug-like compounds that are more active and selective than natural peptides and have fewer side effects. One of the synthetic strategies for obtaining peptidomimetics involves mimicking peptide α-helices, β-sheets or turns. Turns are usually located on the protein surface where they interact with various receptors and are therefore involved in numerous biological events. Among the various synthetic tools for turn mimetic design reported so far, our group uses an approach based on the insertion of different ferrocene templates into the peptide backbone that both induce turn formation and reduce conformational flexibility. Here, we conjugated methyl 1′-aminoferrocene-carboxylate with homo- and heterochiral Pro-Ala dipeptides to investigate the turn formation potential and antiproliferative properties of the resulting peptidomimetics 2–5. Detailed spectroscopic (IR, NMR, CD), X-ray and DFT studies showed that the heterochiral conjugates 2 and 3 were more suitable for the formation of β-turns. Cell viability study, clonogenic assay and cell death analysis showed the highest biological potential of homochiral peptide 4.

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Stereochemistry of α‐aminoisobutyric acid peptides in solution: Helical conformations of protected decapeptides with repeating Aib‐L‐Ala and Aib‐L‐Val sequences

Cited by 50 publications

References 30 publications

Conjugates of 1'-Aminoferrocene-1-carboxylic Acid and Proline: Synthesis, Conformational Analysis and Biological Evaluation

Conjugates of 1'-Aminoferrocene-1-carboxylic Acid and Proline: Synthesis, Conformational Analysis and Biological Evaluation

Hydrogen Bond Patterning and Biological Activity of Ferrocene Conjugates with Homo- and Heterochiral Ala–Pro Dipeptides

Conformational Preferences and Antiproliferative Activity of Peptidomimetics Containing Methyl 1′-Aminoferrocene-1-carboxylate and Turn-Forming Homo- and Heterochiral Pro-Ala Motifs

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