Light and heat control over secondary structure and amyloid-like fiber formation in an overcrowded-alkene-modified Trp zipper

The external photocontrol over peptide folding, by the incorporation of molecular photoswitches into their structure, provides a powerful tool to study biological processes. However, it is limited so far to switches that exhibit only a rather limited geometrical change upon photoisomerization and that show thermal instability of the photoisomer. Here we describe the use of an overcrowded alkene photoswitch to control a model β-hairpin peptide. This photoresponsive unit undergoes a large conformational change and has two thermally stable isomers which has major influence on the secondary structure and the aggregation of the peptide, permitting the phototriggered formation of amyloid-like fibrils.     

Noncovalent Bonds through Sigma and Pi-Hole Located on the Same Molecule. Guiding Principles and Comparisons

Over the last years, scientific interest in noncovalent interactions based on the presence of electron-depleted regions called σ-holes or π-holes has markedly accelerated. Their high directionality and strength, comparable to hydrogen bonds, has been documented in many fields of modern chemistry. The current review gathers and digests recent results concerning these bonds, with a focus on those systems where both σ and π-holes are present on the same molecule. The underlying principles guiding the bonding in both sorts of interactions are discussed, and the trends that emerge from recent work offer a guide as to how one might design systems that allow multiple noncovalent bonds to occur simultaneously, or that prefer one bond type over another.     

Light‐Controlled Histone Deacetylase (HDAC) Inhibitors: Towards Photopharmacological Chemotherapy

Cancer treatment suffers from limitations that have a major impact on the patient’s quality of life and survival. In the case of chemotherapy, the systemic distribution of cytotoxic drugs reduces their efficacy and causes severe side effects due to nonselective toxicity. Photopharmacology allows a novel approach to address these problems because it employs external, local activation of chemotherapeutic agents by using light. The development of photoswitchable histone deacetylase (HDAC) inhibitors as potential antitumor agents is reported herein. Analogues of the clinically used chemotherapeutic agents vorinostat, panobinostat, and belinostat were designed with a photoswitchable azobenzene moiety incorporated into their structure. The most promising compound exhibits high inhibitory potency in the thermodynamically less stable cis form and a significantly lower activity for the trans form, both in terms of HDAC activity and proliferation of HeLa cells. This approach offers a clear prospect towards local photoactivation of HDAC inhibition to avoid severe side effects in chemotherapy.     

Toward stereocontrolled, chemoenzymatic synthesis of unnatural peptides

An efficient, chemoenzymatic method for the multicomponent synthesis of unnatural tripeptides is presented. Development of a previously described procedure combines the diversity offered by multicomponent reactions with the selectivity of biocatalysts and allows the convenient introduction of varied amino acid moieties into the tripeptide scaffold, with control of the stereochemistry. Additionally, it allows the introduction of a methyl group to the amide nitrogen, leading to derivatives of N-methylated amino acids.     

1–D Framework l-arginine zinc(II) units bridged by oxalate: synthesis,structure, properties,and theoretical studies

We synthesized a l-arginine containing Zn²⁺ complex and oxalate ions. {[Zn₂(l-Arg)₂(ox)₂]·8H₂O}_n (1) (l-Arg =l-arginine, ox = oxalate) crystallize in the monoclinic space group P2₁ with a = 8.979(2), b = 9.840(2) (Å), c = 18.509(3) (Å), β = 95.58(3) (Å), V = 1627.6(6) ų, and Z = 2. The zinc centers are six-coordinate via one l-arginine zwitterion and two bridging oxalates. The binuclear [Zn₂(l-Arg)₂(ox)₂] units are linked via oxalate and form 1-D “stair-like” linear chains. The complex was characterized using FT-IR, FT-Raman, UV–vis spectroscopy, and thermal analysis techniques, as well as DFT methods. Electronic bands above 31,000 cm^?1 originate in ^1,3A_u (n→π*) transitions within oxalate ions. Theoretical studies were performed for the model compound {[Zn(l-Arg)(Hox)₂]·4H₂O} using the fragment of the crystallographic structure of 1. The interaction energy (ΔE) values for l-arginine and two oxalate ions are comparable at -145 kcal mol^?1. Natural bond orbital (NBO) analysis of the electronic structure and bonding is also discussed.