Featured
-
-
News & Views |
Complex networks at life’s origins
Explaining the controlled emergence and growth of molecular complexity at life’s origins is one of prebiotic chemistry’s grand challenges. Now, it has been shown that we can observe how the self-organization of a complex carbohydrate network can be modulated by its environment.
- Quentin Dherbassy
- & Kamila B. Muchowska
-
Perspective |
Strategies for developing DNA-encoded libraries beyond binding assays
DNA-encoded libraries can be applied in a diverse range of applications beyond simple binding assays. This Perspective covers the recent progress in using DNA-encoded chemical libraries to investigate complex biological targets and discusses their potential to identify structures that elicit function or possess other useful properties.
- Yiran Huang
- , Yizhou Li
- & Xiaoyu Li
-
Article |
A mating mechanism to generate diversity for the Darwinian selection of DNA-encoded synthetic molecules
DNA-encoded libraries facilitate the discovery of ligands that interact with biomolecules but such technologies do not take full advantage of the principles of Darwinian selection. Now, libraries of conformationally constrained peptides (Dsuprabodies) have been assembled using a strategy that allows for iterative cycles of selection, amplification and diversification. This method was validated with selections against streptavidin and PD-L1.
- Balayeshwanth R. Vummidi
- , Lluc Farrera-Soler
- & Nicolas Winssinger
-
News & Views |
Combining biological and chemical diversity
Phage display enables screening of billions of peptides comprised mainly of natural amino acids. Now, a method to attach and encode a range of structurally diverse compounds has been reported. This method can expand the chemical space covered by phage display peptide libraries.
- Christian Heinis
-
Article |
Selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells
A method to label membrane proteins with a DNA tag has been developed that enables the selection of DNA-encoded chemical libraries against endogenous membrane proteins on live cells. As a demonstration, a 30-million-compound DNA-encoded chemical library is screened against folate receptor, carbonic anhydrase 12 and epidermal growth factor receptor on live cells.
- Yiran Huang
- , Ling Meng
- & Xiaoyu Li
-
Article |
Second-generation DNA-templated macrocycle libraries for the discovery of bioactive small molecules
A second-generation DNA-templated library of 256,000 small-molecule macrocycles has been developed. The improved method was created by streamlining and integrating multiple aspects of DNA-encoded and DNA-templated library synthesis methodology. In vitro selection of the macrocycle library against insulin-degrading enzyme enabled the discovery of potent inhibitors.
- Dmitry L. Usanov
- , Alix I. Chan
- & David R. Liu
-
Article |
Versatile protein recognition by the encoded display of multiple chemical elements on a constant macrocyclic scaffold
Encoded display of multiple chemical elements on a constant macrocyclic scaffold could mimick antibody–antigen recognition. A chemical library constructed using this approach enabled the identification of specific binders against a variety of protein targets, including difficult targets, such as TNF.
- Yizhou Li
- , Roberto De Luca
- & Dario Neri
-
Article |
A protein-targeting strategy used to develop a selective inhibitor of the E17K point mutation in the PH domain of Akt1
It is difficult to develop a selective ligand for point mutations in proteins that are not found in easily addressable locations. Now, an all-chemical, epitope-targeting strategy has been reported, and was used to discover an inhibitory peptide with selectivity for the E17K point mutation in the PH Domain of the Akt1 oncoprotein.
- Kaycie M. Deyle
- , Blake Farrow
- & James R. Heath
-
Article |
Dual-display of small molecules enables the discovery of ligand pairs and facilitates affinity maturation
A method to identify pairs of ligands that simultaneously bind to a target protein has been developed. The method uses two DNA-encoded chemical sub-libraries that self-assemble to form stable dual-display structures, and an encoding system that can be decoded by DNA sequencing and enables both ligands to be identified.
- Moreno Wichert
- , Nikolaus Krall
- & Jörg Scheuermann
-
News & Views |
3D frameworks from 3D printers
High-throughput screening of solvothermal crystallization conditions for MOFs and other solids may receive a boost from the application of 3D printing techniques to low-cost, disposable pressure vessels.
- Ian D. Williams
-
News & Views |
Catalysing dynamic libraries
The composition of dynamic small-molecule libraries can be biased by the addition of a target compound — such as a protein — that binds selectively to one of the components in the mixture. The chemistry of the library must, however, be compatible with the target and it has now been shown that aniline-catalysed exchange of acylhydrazones fits the bill.
- Benjamin L. Miller
-
Article |
Nucleophilic catalysis of acylhydrazone equilibration for protein-directed dynamic covalent chemistry
The composition of a dynamic combinatorial library can be altered by adding a target molecule that either stabilizes (or destabilizes) one or more of its members. The range of reversible chemical reactions compatible with biological targets such as proteins is somewhat limited, but now it has been shown that aniline-catalysed acylhydrazone formation is effective in this context.
- Venugopal T. Bhat
- , Anne M. Caniard
- & Michael F. Greaney