Modular design of synthetic protein mimics. Crystal structure of two seven-residue helical peptide segments linked by .epsilon.-aminocaproic acid

Karle, Isabella L.; Flippen‐Anderson, Judith L.; Sarojadevi, M.; Uma, K.; Balaram, P.

doi:10.1021/ja00010a042

Cited by 64 publications

(35 citation statements)

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“…A checkerboard arrangement has also been found for antiparallel packing, for example, Fig. 7(b) in BocAib-Leu-Aib-Aib-Leu-Leu-Leu-Aib-Leu-Aib-OMe (Katie, Flippen-Anderson, Sukumar & Balaram, 1991). In this case, each helix has four close antiparallel neighbors and four parallel neighbors at a greater distance.…”

Section: Elements Of Assemblymentioning

confidence: 80%

“…The stimulus for this structural study resulted initially from an interest in membrane-active peptides that encapsulate metallic ions (Pinkerton, Steinrauf & Dawkins, 1969), or that form voltage-sensitive ion channels (Mueller & Rudin, 1968;Fox & Richards, 1982;Nagaraj & Balaram, 1981). Subsequently, the design of fourhelix bundles (Hecht, Richardson, Richardson & Ogden, 1990;Hill, Anderson, Wesson, De Grado & Eisenberg, 1990) from helical modules containing Aib residues (Karle, Flippen-Anderson, Sukumar, Uma & Balaram, 1991) and the demonstration of a zipper assembly (Landschulz, Johnson & McKnight, 1988) in the crystalline state (Karle, FlippenAnderson, Uma & Balaram, 1990a) have been additional targets.…”

Section: Introductionmentioning

confidence: 99%

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Folding, aggregation and molecular recognition in peptides

Karle¹

1992

Acta Crystallogr Sect B

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In past years, most of the X-ray structure determinations of oligopeptides were for cyclic peptides or for short linear peptides. Longer peptides usually presented many difficulties in obtaining suitable crystals since the molecules are intrinsically very flexible. More recently, it has been appreciated that the aminoisobutyric acid residue (Aib), which occurs naturally in many peptides of microbial origin, initiates helix folding. Several score of 7-to 15-residue linear peptides containing Aib have been synthesized, crystallized and had their structures determined to high resolution. Many of the peptide structures have been determined in more than one crystalline form. These peptide structures have yielded a plethora of information on types of helices, modes of hydration, water penetration into helical backbones, helices bent by Pro residues, parallel and antiparallel association of helices, effects of Leu residues on association of peptides, an example of a zipper assembly by side chains, and an example of a possible ion channel with a gating mechanism.

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Section: Elements Of Assemblymentioning

confidence: 80%

Section: Introductionmentioning

confidence: 99%

Folding, aggregation and molecular recognition in peptides

Karle¹

1992

Acta Crystallogr Sect B

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“…The use of short polymethylene chains has been investigated using . 103,104 Limited evidence based on interaction with hydrophobic reverse phase C18 columns suggests that these peptides adopt more compact structures in solution. 76 A detailed study of an analogue peptide BocMet-Ala-Leu-Aib-Val-Ala-Acp-Val-Ala-Leu-Aib-ValAla-Phe-OMe has provided evidence for a folded Ushaped arrangement of the two helices in an apolar solvent like chloroform.…”

Section: Design Of Helix±helix Motifsmentioning

confidence: 99%

Stereochemical Control of Peptide Folding

Kaul

Balaram

1999

Bioorganic & Medicinal Chemistry

153

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AbstractÐStereochemically constrained amino acid residues that strongly favour speci®c backbone conformations may be used to nucleate and stabilize speci®c secondary structures in designed peptides. An overview of the use of aa-dialkyl amino acids in stabilizing helical structures in synthetic peptides is presented, with an emphasis on work carried out in the authors laboratory. a-Aminoisobutyric acid (Aib) and related achiral homologs facilitate stable helix formation in oligopeptides as exempli®ed by a large number of crystal structure determinations in the solid state. The ability to design conformationally rigid helical modules has been exploited in attempts to design structurally well characterized helix-linker±helix, using potential nonhelical linking segments. bHairpin design has been approached by exploiting the tendency of`prime turns' to nucleate hairpin formation. The use of nucleating D Pro-Gly segments has resulted in the generation of several well characterized b-hairpin structures, including the crystallographic observation of b-hairpin in a synthetic apolar octapeptide. Extensions of this approach to three stranded b-sheets and larger structures containing multiple D Pro-Gly segments appear readily possible.

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“…1). 25 This arrangement in crystals is stabilized by a continuous chain of intermolecular 'helix-like' hydrogen bonds involving the NH groups of one molecule and the central * E-Mail: pb@mbu.iisc.ernet.in CO groups of a neighboring molecule, which constitute the end of the N-terminal segment and the beginning of the C-terminal segment, respectively. Intramolecular folding would have been expected to yield a U-shaped structure in which the two helices are roughly antiparallel, with an interhelical angle close to 0Њ.…”

Section: -20mentioning

confidence: 99%