Understanding α-amino acid chemistry from X-ray diffraction structures

Toniolo, Claudio; Crisma, Marco; Formaggio, Fernando

doi:10.1002/(sici)1097-0282(1996)40:6<627::aid-bip4>3.0.co;2-y

Cited by 18 publications

(13 citation statements)

References 101 publications

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“…This explanation is based on the generally accepted electron distribution in active esters (18–20). This 3D‐disposition is quite close to those adopted in the crystal state by the related esters Boc‐ l ‐Ala‐ONP o (25) and Tos‐Aib‐ONP o (26). The unique geometry in the molecule of the ‐ONP o esters provides a satisfactory explanation for their special properties (14).…”

Section: Solid‐state Studiessupporting

confidence: 76%

“…X‐ray diffraction analyses combined with spectroscopic/spectrometric investigations provided a large body of valuable information on geometry and conformation of reactive α ‐amino acid and peptide derivatives (26). These parameters, in turn, proved to be quite useful to help our understanding of reactivity, regiospecificity, and racemization tendency of these compounds.…”

Section: Discussionmentioning

confidence: 99%

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On the orange color of Z‐Trp‐ONP_o*

Moretto

Formaggio

Crisma

et al. 2005

The Journal of Peptide Research

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Out of all nitrophenyl esters of N(alpha)-protected alpha-amino acids Z-Trp-ONP(o) is the only one which is deep orange colored in the crystalline state. Any change in N(alpha)-protection, nature of amino acid, spatial separation between Trp and the ester-group or position of the nitro-substitutent in the aromatic ring of the ester function results in a loss of this characteristic property. We solved the molecular and crystal structure of Z-l-Trp-ONP(o) by X-ray diffraction analysis and investigated its color changes and visible (vis) and infrared (IR) absorption spectra in the solid state as a function of the amino acid derivative/KBr (w/w) ratio in the pellets. This investigation was extended to toluene solutions of different Z-Trp-ONP(o) concentrations by use of vis absorption and proton magnetic resonance spectroscopic techniques. The onset of the orange color correlates closely with the appearance of a concentration-dependent absorption band near 500 nm and concentration-dependent shifts of the urethane and indole NH proton resonances. Our observations can be explained by the formation of an intermolecular charge transfer complex involving the Trp indole and the -ONP(o) nitrophenyl as the donor and the acceptor moieties, respectively.

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Section: Solid‐state Studiessupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

On the orange color of Z‐Trp‐ONP_o*

Moretto

Formaggio

Crisma

et al. 2005

The Journal of Peptide Research

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“…Unraveling the relationship between peptide sequence, conformational and physicochemical properties as well as its impact on synthesis and biological function has been a major focus of our research for many years 1–3. In this context, the design and investigation of model peptides exhibiting a high propensity for secondary and tertiary structure formation proved to be ideal targets for elucidating the structural and dynamic parameters governing protein folding and function 4–6. Interestingly, the design of amphiphilic oligopeptides undergoing medium‐induced conformational transitions as a first generation of “switch‐peptides” in the early nineties7, 8 was considered primarily as a contribution to our understanding of the complex mechanism of peptide self‐assembly and folding, whereas its importance as fundamental molecular processes in degenerative diseases has been recognized only more recently 9, 10.…”

Section: Introductionmentioning

confidence: 99%

“…Our laboratory has previously shown that incorporation of molecular switches into polypeptides, based on O,N intramolecular acyl migration in situ, allows for the controlled induction or reversal of secondary structural transitions and self‐assembly of small peptides. Based on the close relationship between the onset of secondary structure and physico‐chemical properties of a growing peptide chain, notably the dramatic decrease in solubility due to self‐association and β‐sheet formation,1–6, 23 the idea of conformationally dissecting the regular amide backbone by insertion of a switch‐element S at appropriate sites (resulting in sequences of chain length below the critical length ( n c , β) for β‐sheet formation) has emerged (Figure 1a).…”

Section: Introductionmentioning

confidence: 99%

Switch‐peptides as folding precursors in self‐assembling peptides and amyloid fibrillogenesis

et al. 2007

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The study of conformational transitions of peptides has obtained considerable attention recently because of their importance as a molecular key event in a variety of degenerative diseases. However, the study of peptide selfassembly into β‐sheets and amyloid β (Aβ) fibrils is strongly hampered by their difficult synthetic access and low solubility. We have recently developed a new concept termed “switch‐peptides” that allows the controlled onset of polypeptide folding and misfolding at physiologic conditions. As a major feature, the folding process is initiated by chemically or enzyme triggered O,N‐acyl migration in flexible and soluble folding precursors containing Ser‐ or Thr‐derived switch (S)‐elements. The elaborated methodologies are exemplified for the in situ conversion of NPY‐ and Cyclosporine A‐derived prodrugs, as well as for the onset and reversal of α and β conformational transitions in Aβ peptides. In combining orthogonally addressable switch‐elements, the consecutive switching on of S‐elements gives new insights into the role of individual peptide segments (“hot spots”) in early processes of polypeptide self‐assembly and fibrillogenesis. Finally, the well‐known secondary structure disrupting effect of pseudoprolines (ΨPro) is explored for its use as a building block (S‐element) in switch‐peptides. To this end, synthetic strategies are described, allowing for the preparation of Ψ Pro‐containing folding precursors, exhibiting flexible random‐coil conformations devoid of fibril forming propensity. The onset of β‐sheet and fibril formation by restoring the native peptide chain in a single step classify Ψ Pro‐units as the most powerful tool for inhibiting peptide self‐assembly, and complement the present methodologies of the switch‐concept for the study of fibrillogenesis. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 239–252, 2007. This article was originally published online as an accepted preprint. The ‘Published Online’ date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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“…The introduction of a,a-dialkyl-a-amino acids into peptide sequences results in significant restriction of the available range of backbone conformations [1,2]. Several achiral C~,C~-dialkyl glycines (H2N-CRIR2-COOH) with linear substitutents (like a-aminoisobutyric acid (Aib), diethylglycine (Deg), dipropylglycine (Dpg), dibutylglycine (Dbg)), cyclic substitutents (like Acnc'S where 'n' is the number of carbon atoms in the cycloalkane ring; 1-aminocyclopentane-l-carboxylic acid (Acsc), 1-aminocyclo-hexane-l-carboxylic acid (Ac6c), 1aminocycloheptane-l-carboxylic acid (Ac7c)) and aromatic substitutents (like diphenylglycine, dibenzylglycine) have been synthesized [4]. Several achiral C~,C~-dialkyl glycines (H2N-CRIR2-COOH) with linear substitutents (like a-aminoisobutyric acid (Aib), diethylglycine (Deg), dipropylglycine (Dpg), dibutylglycine (Dbg)), cyclic substitutents (like Acnc'S where 'n' is the number of carbon atoms in the cycloalkane ring; 1-aminocyclopentane-l-carboxylic acid (Acsc), 1-aminocyclo-hexane-l-carboxylic acid (Ac6c), 1aminocycloheptane-l-carboxylic acid (Ac7c)) and aromatic substitutents (like diphenylglycine, dibenzylglycine) have been synthesized [4].…”

Section: Introductionmentioning

confidence: 99%