Helix induction potential of N-terminal α-methyl, α-amino acids

Gobbo, Marina; Biondi, Laura; Filira, Fernando; Formaggio, Fernando; Crisma, Marco; Rocchi, Raniero; Toniolo, Claudio; Broxterman, Quirinus B.; Kamphuis, J.

doi:10.1007/bf02443448

Cited by 9 publications

(9 citation statements)

References 9 publications

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“…the hydrophobic moment relative to that of a maximally amphipathic peptide; δ, angle subtended by hydrophobic sector; %α, percent helix content. b The percent helix content of peptides containing Aib cannot be precisely determined as this residue is not chiral [33]. c Results are the mean of three independent trials run in duplicate.…”

Section: Resultsmentioning

confidence: 99%

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Amphipathic α helical antimicrobial peptides.

Giangaspero

Sandri

Tossi

2001

European Journal of Biochemistry

447

276

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Antimicrobial peptides (AMPs) that assume an amphipathic alpha helical structure are widespread in nature. Their activity depends on several parameters including the sequence, size, degree of structure formation, cationicity, hydrophobicity and amphipathicity. The analysis of numerous natural AMPs provided representative values for these parameters and led to a sequence template with which to generate potent artificial lead AMPs. Sequences were then varied in a rational manner, using both natural and nonproteinogenic amino acids, to probe the individual roles of each parameter in modulating biological activity. A high cationicity combined with a stabilized amphipathic alpha helical structure conferred enhanced cidal activity towards all the cell types considered, and was a requirement for Gram-positive bacteria and fungi. An elevated helicity also correlated with increased hemolytic activity. The structural requirements for activity against several Gram-negative bacteria were instead considerably less stringent, so that it persisted in peptides in which formation of a helical structure and/or amphipathicity were impeded. Either a reduced charge or a reduced hydrophobicity resulted in generally inactive peptides. These observations, combined with the kinetics of bacterial membrane permeabilization and time-killing are discussed in terms of currently accepted models of action for this type of peptide. The simple guidelines obtained in this study allowed the design of highly active shortened AMPs and may be generally useful in the development of this type of peptides as anti-infective agents.

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Section: Resultsmentioning

confidence: 99%

“… b The percent helix content of peptides containing Aib can only be approximately estimated as this residue is achiral (see [33]). …”

Section: Resultsmentioning

confidence: 99%

Amphipathic α helical antimicrobial peptides.

Giangaspero

Sandri

Tossi

2001

European Journal of Biochemistry

447

276

View full text Add to dashboard Cite

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“…The role of helicity (propensity for assuming an a helical structure) was tested by introducing either helix-stabilizing factors, such as aminoisobutyric (Aib, B) residues [33] [P19(5|B) and P19(9|B)] or Glu/Orn salt bridging [P19(6|E)] or helix-inhibiting factors, such as two proline residues in key sequence positions [19(6|P) Fig. 2).…”

Section: Peptide Designmentioning

confidence: 99%

“…It also, however, results in an increased ability to lyse erythrocytes. Unfortunately, as Aib is not chiral, it is difficult to precisely determine the extent of helix stabilization using CD spectroscopy [33], and the estimate in Table 2 is conservative.…”

Section: Peptide Designmentioning

confidence: 99%

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Amphipathic alpha helical antimicrobial peptides. . A systematic study of the effects of structural and physical properties on biological activity

Giangaspero¹,

Sandri²,

Tossi³

2001

Eur J Biochem

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Control of peptide conformation by the Thorpe-Ingold effect (C?-tetrasubstitution)

et al. 2001

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The preferred conformations of peptides heavily based on the currently extensively exploited achiral and chiral α‐amino acids with a quaternary α‐carbon atom, as determined by conformational energy computations, crystal‐state (x‐ray diffraction) analyses, and solution (1H‐NMR and spectroscopic) investigations, are reviewed. It is concluded that 310/α‐helical structures and the fully extended (C5) conformation are preferentially adopted by peptide sequences characterized by this family of amino acids, depending upon overall bulkiness and nature (e.g., whether acyclic or C αi ↔ C αitalici cyclized) of their side chains. The intriguing relationship between α‐carbon chirality and bend/helix handedness is also illustrated. γ‐Bends and semiextended conformations are rarely observed. Formation of β‐sheet structures is prevented. © 2002 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 60: 396–419, 2001

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Helix induction potential of N-terminal α-methyl, α-amino acids

Cited by 9 publications

References 9 publications

Amphipathic α helical antimicrobial peptides.

Amphipathic α helical antimicrobial peptides.

Amphipathic alpha helical antimicrobial peptides. . A systematic study of the effects of structural and physical properties on biological activity

Control of peptide conformation by the Thorpe-Ingold effect (C?-tetrasubstitution)

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