Protein Segments with Conformationally Restricted Amino Acids Can Control Supramolecular Organization at the Nanoscale

Zanuy, David; Ballano, Gema; Jiménez, Ana I.; Casanovas, Jordi; Haspel, Nurit; Cativiela, Carlos; Curcó, David; Nussinov, Ruth; Alemán, Carlos

doi:10.1021/ci9001487

Cited by 13 publications

(9 citation statements)

References 60 publications

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“…Those new spectroscopic properties [41] can be used as biosensors, spectroscopic or biophysical probes, or even for building new nanosystems for drug delivery and diagnosis through imaging to be used in medicine [34,40,42,43]. Other applications of Nc-aa are their use in nanobiology to promote the self-assembly of nanostructures [44,45] or for developing bioinspired synthetic organic polymers that emulate the shape and properties of natural peptides and proteins [46,47].…”

Section: Nonstandard Amino Acidsmentioning

confidence: 99%

A Protocol for the Design of Protein and Peptide Nanostructure Self-Assemblies Exploiting Synthetic Amino Acids

Haspel

Zheng

Alemán

et al. 2016

Methods in Molecular Biology

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In recent years there has been increasing interest in nanostructure design based on the self-assembly properties of proteins and polymers. Nanodesign requires the ability to predictably manipulate the properties of the self-assembly of autonomous building blocks, which can fold or aggregate into preferred conformational states. The design includes functional synthetic materials and biological macromolecules. Autonomous biological building blocks with available 3D structures provide an extremely rich and useful resource. Structural databases contain large libraries of protein molecules and their building blocks with a range of sizes, shapes, surfaces, and chemical properties. The introduction of engineered synthetic residues or short peptides into these building blocks can greatly expand the available chemical space and enhance the desired properties. Herein, we summarize a protocol for designing nanostructures consisting of self-assembling building blocks, based on our recent works. We focus on the principles of nanostructure design with naturally occurring proteins and synthetic amino acids, as well as hybrid materials made of amyloids and synthetic polymers.

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Section: Nonstandard Amino Acidsmentioning

confidence: 99%

A Protocol for the Design of Protein and Peptide Nanostructure Self-Assemblies Exploiting Synthetic Amino Acids

Haspel

Zheng

Alemán

et al. 2016

Methods in Molecular Biology

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“…Within that context, a specific family of non-coded amino acids, the 1-aminocycloalkane-1carboxylic acids 18,19 (known in the abbreviated form as Ac n c, with n referring to the ring size), have been recently proposed as a structural tool for conformational control and enhancement of naturally occurring structural motifs. [19][20][21][22][23] This series of residues exhibits a restricted conformational space characterized by a high propensity to adopt φ, ψ backbone angles typical of the 3 10 -/α-helix (with some distortion in the case of Ac 3 c). [23][24][25] As we previously mentioned, in the majority of the most favored CREKA conformations Arg is at position i + 1 of a β-turn motif.…”

Section: Introductionmentioning

confidence: 99%

“…[19][20][21][22][23] This series of residues exhibits a restricted conformational space characterized by a high propensity to adopt φ, ψ backbone angles typical of the 3 10 -/α-helix (with some distortion in the case of Ac 3 c). [23][24][25] As we previously mentioned, in the majority of the most favored CREKA conformations Arg is at position i + 1 of a β-turn motif. 10 In such arrangements, the backbone dihedral angles adopted by the residue are in the regions corresponding to the aforementioned helical structures.…”

Section: Introductionmentioning

confidence: 99%

Exploring the energy landscape of a molecular engineered analog of a tumor-homing peptide

Revilla-López

Torras

Nussinov

et al. 2011

Phys. Chem. Chem. Phys.

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Recently a new non-coded amino acid was designed as a replacement for Arg, to protect the tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) from proteases. This constrained Arg analog, denoted c(5)Arg, was engineered to also promote the stability of the CREKA bioactive conformation. The conformational profile of the CREKA analog obtained by replacing Arg by c(5)Arg has been extensively investigated in this work. Two molecular dynamics simulations-based strategies have been employed: a modified simulated annealing and replica exchange. Results obtained using both techniques show that the conformational features of the new analog fulfill the purpose of its design. The new CREKA analog not only preserves the main structural attributes found for the bioactive conformation of the parent peptide but also shows lower flexibility. Moreover, the conformational profile of the mutated peptide narrows towards the most stable structures previously observed for the parent CREKA peptide.

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“…Some of these nc‐aa are present in nature, occurring in nonribosomally produced peptides (e.g., antibiotics); however, most are synthesized by chemists. Among the latter, those used for protein engineering1–6 and nanobiology7–12 are particularly interesting, and their applications extend to many fields such as pharmacology (drug design),13, 14 biotechnology (biosensors),15, 16 and nanomedicine (systems for drug delivery and diagnosis through imaging) 17, 18…”

Section: Introductionmentioning

confidence: 99%

Integrating the intrinsic conformational preferences of noncoded α‐amino acids modified at the peptide bond into the noncoded amino acids database

et al. 2011

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Recently, we reported a database (NCAD, Non-Coded Amino acids Database; http://recerca.upc.edu/imem/index.htm) that was built to compile information about the intrinsic conformational preferences of non-proteinogenic residues determined by quantum mechanical calculations, as well as bibliographic information about their synthesis, physical and spectroscopic characterization, the experimentally-established conformational propensities, and applications (J. Phys. Chem. B 2010, 114, 7413). The database initially contained the information available for α-tetrasubstituted α-amino acids. In this work, we extend NCAD to three families of compounds, which can be used to engineer peptides and proteins incorporating modifications at the –NHCO– peptide bond. Such families are: N-substituted α-amino acids, thio-α-amino acids, and diamines and diacids used to build retropeptides. The conformational preferences of these compounds have been analyzed and described based on the information captured in the database. In addition, we provide an example of the utility of the database and of the compounds it compiles in protein and peptide engineering. Specifically, the symmetry of a sequence engineered to stabilize the 310-helix with respect to the α-helix has been broken without perturbing significantly the secondary structure through targeted replacements using the information contained in the database.

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Protein Segments with Conformationally Restricted Amino Acids Can Control Supramolecular Organization at the Nanoscale

Cited by 13 publications

References 60 publications

A Protocol for the Design of Protein and Peptide Nanostructure Self-Assemblies Exploiting Synthetic Amino Acids

A Protocol for the Design of Protein and Peptide Nanostructure Self-Assemblies Exploiting Synthetic Amino Acids

Exploring the energy landscape of a molecular engineered analog of a tumor-homing peptide

Integrating the intrinsic conformational preferences of noncoded α‐amino acids modified at the peptide bond into the noncoded amino acids database

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