Computational study of the conformational preferences of the (R)‐8‐amino‐pentacyclo[5.4.0.02,6.03,10.05,9] undecane‐8‐carboxylic acid monopeptide

Bisetty, Krishna; Gómez‐Catalán, Jesús; Alemán, Carlos; Giralt, Ernest; Kruger, Hendrik G.; Pérez, Juan J.

doi:10.1002/psc.526

Cited by 18 publications

(18 citation statements)

References 30 publications

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“…Interestingly, the overall shape of these plots closely resembles those previously obtained for the PCU cage peptide 15 shown in Figures 4 and 5. Energies of the plots are expressed in kcal mol -1 relative to the lowest energy minimum in each case, and contours are plotted every 2 kcal mol -1 .…”

Section: Resultssupporting

confidence: 78%

“…therefore expected that both cage structures will induce the same conformational constraints when experimentally incorporated in nonnatural peptides. The conformational space of Ac-Tris-NHMe was compared with our previous results, 15,16 including Ac-PCU-NHMe, Ac-Ala-NHMe, Ac-Gly-NHMe, and Ac-Aib-NHMe (see Supplementary Material). Glycine tends to favor extended conformations and alanine exhibit some helical conformations, while the conformations of aminoisobutyric acid 16,[32][33][34] are very similar to that exhibited by Ac-Tris-NHMe.…”

Section: Figurementioning

confidence: 99%

“…15 Energies are expressed in kcal mol -1 relative to the lowest energy minimum, and the contours are plotted every 2 kcal mol between the AMBER (parm94) and the HF/6-31G* level fall between a range of 2 to 158.…”

Section: Figurementioning

confidence: 99%

“…15 Energies are expressed in kcal mol -1 relative to the lowest energy minimum, and the contours are plotted every 2 kcal mol …”

Section: Figurementioning

confidence: 99%

“…This is a logical extension of our conformational studies on the PCU cage dipeptide (4b) as the model compound. [14][15][16] We have concluded that the PCU cage residue exhibits preferences for helical conformations as well as induces promising -turn [17][18][19] characteristics. A nonrelated experimental and computational investigation on peptide analogues containing a PCU scaffold was recently published.…”

Section: Introductionmentioning

confidence: 98%

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Analysis of the conformational profile of trishomocubane amino acid dipeptide

Bisetty¹,

Govender²,

Kruger³

2005

Biopolymers

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4-Amino-(D3)-trishomocubane-4-carboxylic acid is a constrained alpha-amino acid residue that exhibits promising conformational characteristics, i.e., helical and beta-turns. As part of the development of conformational guidelines for the design of peptides and protein surrogates, the conformational energy calculations on trishomocubane using molecular mechanics and ab initio methods are presented. The C(alpha) carbon of trishomocubane forms part of the cyclic structure, and consequently a peptidic environment was simulated with an acetyl group on its N-terminus and a methylamide group on its C-terminus. Ramachandran maps computed at the molecular mechanics level using the standard AMBER (parm94) force field libraries compared reasonably well with the corresponding maps computed at the Hartree Fock level, using the 6-31G* basis set. Trishomocubane peptide (Ac-Tris-NHMe) is characterized by four low energy conformers corresponding to the C7ax, C7eq, 3(10), and alpha(L) helical structures.

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Section: Resultssupporting

confidence: 78%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

“…15 Energies are expressed in kcal mol -1 relative to the lowest energy minimum, and the contours are plotted every 2 kcal mol …”

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

See 3 more Smart Citations

Analysis of the conformational profile of trishomocubane amino acid dipeptide

Bisetty¹,

Govender²,

Kruger³

2005

Biopolymers

Self Cite

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A theoretical study of pentacyclo‐undecane cage peptides of the type [Ac‐X‐Y‐NHMe]

Bisetty

Corcho²,

Cantó³

et al. 2005

Journal of Peptide Science

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The conformational preferences of peptides of the type, Ac-X-Y-NHMe, where X and Y = Ala, cage and Pro, were studied by means of computational techniques within the framework of a molecular mechanics approach. For each of the eight peptide analogues, extensive conformational searches were carried out using molecular dynamics (MD) and simulated annealing (SA) protocols in an iterative fashion. Both results are in good agreement and complement each other. The conformational search indicates that the cage residue restricts the conformational freedom of the dipeptide considerably in comparison with the other model residues used. This study revealed that proline exhibits a greater tendency in promoting reverse-turn characteristics in comparison to the cage peptides, which show promising beta-turn characteristics. It was also found that 300-500 K is not sufficient to overcome rotational barriers for cage peptides. In all cases, the low-energy conformers have a tendency to form bent structures.

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Structure-based approach to the design of BakBH3 mimetic peptides with increased helical propensity

2013

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The Bcl-2 family of proteins are well-characterized regulators of the intrinsic apoptotic pathway. Proteins within this family can be classified as either prosurvival or prodeath members and the balance between them present at the mitochondrial membrane is what determines if the cell lives or dies. Specific interactions among Bcl-2 family proteins play a crucial role in regulating programmed cell death. Structural studies have established a conserved interaction pattern among Bcl-2 family members. This interaction is mediated by the binding of the hydrophobic face of the amphipathic α-helical BH3 domain into a conserved hydrophobic groove on the prosurvival partners. It has been reported that an increase in the helical content of BH3 mimetic peptides considerably improves the binding affinity. In this context, this work states for designing peptides derived from the BH3 domain of the proapoptotic protein Bak by substitution of some non-interacting residues by the helical inducing residue Aib. Different synthetic peptides preserving BakBH3 relevant interactions were proposed and simulated presenting a better predicted binding energy and higher helical content than the wild type Bak peptide.

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Computational study of the conformational preferences of the (R)‐8‐amino‐pentacyclo[5.4.0.0^2,6.0^3,10.0^5,9] undecane‐8‐carboxylic acid monopeptide

Cited by 18 publications

References 30 publications

Analysis of the conformational profile of trishomocubane amino acid dipeptide

Analysis of the conformational profile of trishomocubane amino acid dipeptide

A theoretical study of pentacyclo‐undecane cage peptides of the type [Ac‐X‐Y‐NHMe]

Structure-based approach to the design of BakBH3 mimetic peptides with increased helical propensity

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