scholarly journals Stapling of unprotected helical peptides via photo-induced intramolecular thiol–yne hydrothiolation

2016 ◽  
Vol 7 (5) ◽  
pp. 3325-3330 ◽  
Author(s):  
Yuan Tian ◽  
Jingxu Li ◽  
Hui Zhao ◽  
Xiangze Zeng ◽  
Dongyuan Wang ◽  
...  
Keyword(s):  
Uv Irradiation ◽  
Functional Group ◽  
Helical Conformation ◽  
Stapled Peptides ◽  
Helical Peptides ◽  
Rapid Access

A one component intramolecular thiol–yne macrocyclization is achieved upon UV irradiation to constrain short unprotected peptides into a helical conformation, providing rapid access to stapled peptides with satisfying functional group tolerance.

Rh(III)-catalyzed annulated coupling of sulfoxonium ylides and iodonium ylides: a rapid access to isocoumarins

2022 ◽  
Author(s):  
Chuanliu Yin ◽  
Lianghao Li ◽  
Chuanming Yu
Keyword(s):  
Functional Group ◽  
Direct Synthesis ◽  
Rapid Access ◽  
Iodonium Ylides

Direct synthesis of isocoumarin skeletons has been realized through Rh(III)-Catalyzed [3 + 3] annulation of sulfoxonium ylides and iodonium carbenes. The synthetic protocol constructed efficiently with the broad functional group...

scholarly journals Non-linearity of the collagen triple helix in solution and implications for collagen function

2017 ◽  
Vol 474 (13) ◽  
pp. 2203-2217 ◽  
Author(s):  
Kenneth T. Walker ◽  
Ruodan Nan ◽  
David W. Wright ◽  
Jayesh Gor ◽  
Anthony C. Bishop ◽  
...  
Keyword(s):  
Analytical Ultracentrifugation ◽  
Linear Structure ◽  
Small Degree ◽  
Scattering Data ◽  
Helical Conformation ◽  
End Effects ◽  
Helical Peptides ◽  
Atomistic Modelling ◽  
Triple Helices ◽  
Dynamics Simulations

Collagen adopts a characteristic supercoiled triple helical conformation which requires a repeating (Xaa-Yaa-Gly)n sequence. Despite the abundance of collagen, a combined experimental and atomistic modelling approach has not so far quantitated the degree of flexibility seen experimentally in the solution structures of collagen triple helices. To address this question, we report an experimental study on the flexibility of varying lengths of collagen triple helical peptides, composed of six, eight, ten and twelve repeats of the most stable Pro-Hyp-Gly (POG) units. In addition, one unblocked peptide, (POG)10unblocked, was compared with the blocked (POG)10 as a control for the significance of end effects. Complementary analytical ultracentrifugation and synchrotron small angle X-ray scattering data showed that the conformations of the longer triple helical peptides were not well explained by a linear structure derived from crystallography. To interpret these data, molecular dynamics simulations were used to generate 50 000 physically realistic collagen structures for each of the helices. These structures were fitted against their respective scattering data to reveal the best fitting structures from this large ensemble of possible helix structures. This curve fitting confirmed a small degree of non-linearity to exist in these best fit triple helices, with the degree of bending approximated as 4–17° from linearity. Our results open the way for further studies of other collagen triple helices with different sequences and stabilities in order to clarify the role of molecular rigidity and flexibility in collagen extracellular and immune function and disease.

scholarly journals Incorporation of Putative Helix-Breaking Amino Acids in the Design of Novel Stapled Peptides: Exploring Biophysical and Cellular Permeability Properties

Molecules ◽  
2019 ◽  
Vol 24 (12) ◽  
pp. 2292 ◽  
Author(s):  
Anthony W. Partridge ◽  
Hung Yi Kristal Kaan ◽  
Yu-Chi Juang ◽  
Ahmad Sadruddin ◽  
Shuhui Lim ◽  
...  
Keyword(s):  
Amino Acids ◽  
Amino Acid ◽  
Binding Affinity ◽  
Amino Acid Substitutions ◽  
Cellular Activity ◽  
Stapled Peptides ◽  
Helical Peptides ◽  
High Affinity ◽  
Cellular Permeability ◽  
Target Binding

Stapled α-helical peptides represent an emerging superclass of macrocyclic molecules with drug-like properties, including high-affinity target binding, protease resistance, and membrane permeability. As a model system for probing the chemical space available for optimizing these properties, we focused on dual Mdm2/MdmX antagonist stapled peptides related to the p53 N-terminus. Specifically, we first generated a library of ATSP-7041 (Chang et al., 2013) analogs iteratively modified by L-Ala and D-amino acids. Single L-Ala substitutions beyond the Mdm2/(X) binding interfacial residues (i.e., Phe3, Trp7, and Cba10) had minimal effects on target binding, α-helical content, and cellular activity. Similar binding affinities and cellular activities were noted at non-interfacial positions when the template residues were substituted with their d-amino acid counterparts, despite the fact that d-amino acid residues typically ‘break’ right-handed α-helices. d-amino acid substitutions at the interfacial residues Phe3 and Cba10 resulted in the expected decreases in binding affinity and cellular activity. Surprisingly, substitution at the remaining interfacial position with its d-amino acid equivalent (i.e., Trp7 to d-Trp7) was fully tolerated, both in terms of its binding affinity and cellular activity. An X-ray structure of the d-Trp7-modified peptide was determined and revealed that the indole side chain was able to interact optimally with its Mdm2 binding site by a slight global re-orientation of the stapled peptide. To further investigate the comparative effects of d-amino acid substitutions we used linear analogs of ATSP-7041, where we replaced the stapling amino acids by Aib (i.e., R84 to Aib4 and S511 to Aib11) to retain the helix-inducing properties of α-methylation. The resultant analog sequence Ac–Leu–Thr–Phe–Aib–Glu–Tyr–Trp–Gln–Leu–Cba–Aib–Ser–Ala–Ala–NH2 exhibited high-affinity target binding (Mdm2 Kd = 43 nM) and significant α-helicity in circular dichroism studies. Relative to this linear ATSP-7041 analog, several d-amino acid substitutions at Mdm2(X) non-binding residues (e.g., d-Glu5, d-Gln8, and d-Leu9) demonstrated decreased binding and α-helicity. Importantly, circular dichroism (CD) spectroscopy showed that although helicity was indeed disrupted by d-amino acids in linear versions of our template sequence, stapled molecules tolerated these residues well. Further studies on stapled peptides incorporating N-methylated amino acids, l-Pro, or Gly substitutions showed that despite some positional dependence, these helix-breaking residues were also generally tolerated in terms of secondary structure, binding affinity, and cellular activity. Overall, macrocyclization by hydrocarbon stapling appears to overcome the destabilization of α-helicity by helix breaking residues and, in the specific case of d-Trp7-modification, a highly potent ATSP-7041 analog (Mdm2 Kd = 30 nM; cellular EC50 = 600 nM) was identified. Our findings provide incentive for future studies to expand the chemical diversity of macrocyclic α-helical peptides (e.g., d-amino acid modifications) to explore their biophysical properties and cellular permeability. Indeed, using the library of 50 peptides generated in this study, a good correlation between cellular permeability and lipophilicity was observed.

α-d-Galacturonic Acid as Natural Ligand for Selective Copper-Catalyzed N-Arylation of N-Containing Heterocycles

Synlett ◽  
2019 ◽  
Vol 30 (19) ◽  
pp. 2173-2180
Author(s):  
Chunling Yuan ◽  
Yingdai Zhao ◽  
Li Zheng
Keyword(s):  
Galacturonic Acid ◽  
Functional Group ◽  
Aryl Halides ◽  
Donor Ligand ◽  
Arylboronic Acids ◽  
Rapid Access ◽  
Natural Ligand ◽  
Acid Hydrate

The first application of α-d-galacturonic acid hydrate (GalA) is reported here, as a potential O-donor ligand. The C–N couplings of N-heterocycles with aryl halides or arylboronic acids could be readily conducted and exhibited good functional group tolerance with characters of selectivity. These N-arylazoles allow rapid access to several pharmaceutical intermediates and can be easily transformed into a variety of other interesting scaffolds as well.

scholarly journals (4+3)-cycloaddition chemists of oxidopyridinium ions and related study

2019 ◽  
Author(s):  
◽  
Chencheng Fu
Keyword(s):  
Uv Radiation ◽  
Photochemical Reaction ◽  
Functional Group ◽  
Cycloaddition Reaction ◽  
Product Yield ◽  
Membered Ring ◽  
Starting Material ◽  
Unsaturated Ester ◽  
Rapid Access ◽  
Cyclobutane Ring

The (4+3)-cycloaddition reaction is a cycloaddition between a 4-atom species and a 3-atom species to form a seven-membered ring. This reaction results in the formation of seven-membered rings. Our research expanded the scope of (4+3)-cycloaddition reaction by using the oxidopyridinium species as the dienophile -- the 3-atom species. By adding an electron-withdrawing functional group to the starting material, we were be able to get good to excellent product yield. The process provides rapid access to bicyclic nitrogenous structures resembling natural alkaloids. [2+2]-Photocycloaddition is a cycloaddition between two olefins to form a cyclobutane ring. The intramolecular [2+2]-cycloaddition of nitrogen-substituted alkenes can be employed to make complicated alkaloids. Our previous work made the 7-azabicyclo[4.3.1]deca-3,8-diene skeleton, which is a nice substrate for the cycloaddition. Under UV radiation, the heteroatom-substituted unsaturated ester undergoes intramolecular [2+2]-cycloaddition with the cyclic alkene to make a cage-like ketone in good to excellent yield, giving rise to a rigid tropane-like alkaloid skeleton. The scope and mechanism of the photochemical reaction will be discussed.

Rapid access to difluoroalkylated pyrrolobenzodiazepines via a Pd-catalyzed C–H difluoroalkylation/cyclization cascade reaction

2019 ◽  
Vol 6 (3) ◽  
pp. 410-414 ◽  
Author(s):  
Yang Gao ◽  
Chunpu Li ◽  
Bin Xu ◽  
Hong Liu
Keyword(s):  
Functional Group ◽  
Cascade Reaction ◽  
Efficient Approach ◽  
Rapid Access ◽  
Two Component ◽  
Component C

An efficient approach to difluoroalkylated pyrrolobenzodiazepines has been developed using a Pd-catalyzed two-component C–H difluoroalkylation/cyclization cascade reaction in good yields with excellent functional group tolerance.

Effects of Ultraviolet (UV) Treatment on the Properties of Black Tilapia Fish Skins Gelatin

2020 ◽  
Vol 1010 ◽  
pp. 465-470
Author(s):  
Norhasikin Ismail ◽  
Maizlinda Izwana Idris ◽  
Hasan Zuhudi Abdullah
Keyword(s):  
Contact Angle ◽  
Fourier Transform ◽  
Infrared Spectroscopy ◽  
Water Contact Angle ◽  
Uv Irradiation ◽  
Functional Group ◽  
Gel Strength ◽  
Fish Gelatin ◽  
Uv Treatment ◽  
Water Contact

The aim of the study is to investigate the effects of ultraviolet (UV) treatment on the properties of black tilapia fish skins gelatin. The fish gelatin were investigated in terms of gel strength, functional group and the water contact angle of the gelatin. The UV treatment were irradiated with UVA and UVC at different time (0.5, 1.0, 1.5 and 2.0 h). The gel strength of gelatin gel significantly increases after UV irradiation for both UVA and UVC sample. The water contact angle of the gelatin was categorized as hydrophobic for both gelatin that treated with UVA and UVC which the angle >65°. The interactions and characteristic of functional groups for gelatin that treated with UV were analyzed via Fourier Transform Infrared Spectroscopy (FTIR). Results indicated that employing UV irradiation as an alternative method to enhance some of the quality attributes of fish gelatin.

The effect of thiol functional group incorporation into cationic helical peptides on antimicrobial activities and spectra

Biomaterials ◽  
2011 ◽  
Vol 32 (34) ◽  
pp. 9100-9108 ◽  
Author(s):  
Nikken Wiradharma ◽  
Majad Khan ◽  
Lin-Kin Yong ◽  
Charlotte A.E. Hauser ◽  
See Voon Seow ◽  
...  
Keyword(s):  
Functional Group ◽  
Antimicrobial Activities ◽  
Helical Peptides

Stimuli-responsive conformational transformation of antimicrobial peptides stapled with an azobenzene unit

2020 ◽  
Vol 44 (35) ◽  
pp. 14777-14780
Author(s):  
Jeonghun Lee ◽  
Hanwool Lee ◽  
Chulhee Kim
Keyword(s):  
Antimicrobial Peptides ◽  
Uv Irradiation ◽  
Reductive Cleavage ◽  
Helical Conformation ◽  
Conformational Transformation ◽  
Stimuli Responsive

The effect of the azobenzene-stapling position on the triggered transformation of the helical conformation of KLA peptides in response to UV irradiation and reductive cleavage is investigated.

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