Folding, aggregation and molecular recognition in peptides

Abstract

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.

Specific neurotrophin binding to leucine‐rich motif peptides of TrkA and TrkB

“…in terms of the underlying highly specific biochemical mechanism, the observed binding phenomena apparently can not quantitatively account for the binding affinity observed in vivo [3,22,25,34] or using recombinant receptor proteins [39]. It must therefore be assumed that the capacity of the columns was aggravated by the fact that a large percentage of the peptides was either coupled to the matrix in a way that abolished binding affinity or was simply folded in an incorrect fashion [4,10,20]. Some peptides only exhibit a weak tendency to adopt a defined tertiary structure so that in a steady state balance only a small number of peptides exists in an active form at a given time point [10].…”

“…It must therefore be assumed that the capacity of the columns was aggravated by the fact that a large percentage of the peptides was either coupled to the matrix in a way that abolished binding affinity or was simply folded in an incorrect fashion [4,10,20]. Some peptides only exhibit a weak tendency to adopt a defined tertiary structure so that in a steady state balance only a small number of peptides exists in an active form at a given time point [10]. Furthermore, there are prominent examples of peptides that need the support of carrier proteins in order to acquire the correct conformation and thus function properly [33,37].…”

Facile transition between 310‐ and α‐helix: Structures of 8‐, 9‐, and 10‐residue peptides containing the ‐(Leu‐Aib‐Ala)2‐Phe‐Aib‐fragment

“…In apolar helices, no specific side chains attract each other. The dominating factor in the packing motifs is shape selection with bulges fitting into grooves (Karle, 1992;.…”

“…Those with more than 10 residues prefer to form mixed 310-/a-, or a-helices . Figure 1 shows the relationship between helix type as a function of the number of Aib residues with respect to the total number of residues in a peptide Karle, 1992). The information for the graph has been obtained from welldetermined crystal structures with resolutions of -0.9 A.…”

Infinite pleated β-sheet formed by the β-hairpin Boc-β-Phe-β-Phe- d -Pro-Gly-β-Phe-β-Phe-OMe

“…The two common secondary structures adopted by polypeptide backbones, helices and sheets, can be generated in designed synthetic oligopeptides, which can then self-assemble into crystalline arrays (1). Peptide helices in hydrophobic sequences readily form single crystals in which cylindrical molecules pack into columnar arrangements, either parallel or antiparallel, while head-to-tail hydrogen bonds are formed between adjacent molecules in an individual column (2). Adjacent columns are held together in three dimensions by van der Waals forces.…”