Peptidomimetic bond formation by DNA-templated acyl transfer

McKee, Mireya L.; Evans, Amanda C.; Gerrard, Simon R.; O’Reilly, Rachel K.; Turberfield, Andrew J.; Stulz, Eugen

doi:10.1039/c0ob00753f

Cited by 31 publications

(18 citation statements)

References 45 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“… 17 The limited stability of the activated ester BBs in solution can cause problems, however. 22 , 23 Wittig olefination results in the formation of a carbon–carbon double bond, so allows the exploration of a different region of chemical space. It has been used for DTS of macrocycles 24 − 27 and linear oligomers (see ref ( 22 ) for a recent example).…”

Section: Dna-templated Chemistrymentioning

confidence: 99%

The Evolution of DNA-Templated Synthesis as a Tool for Materials Discovery

2017

Self Cite

View full text Add to dashboard Cite

ConspectusPrecise control over reactivity and molecular structure is a fundamental goal of the chemical sciences. Billions of years of evolution by natural selection have resulted in chemical systems capable of information storage, self-replication, catalysis, capture and production of light, and even cognition. In all these cases, control over molecular structure is required to achieve a particular function: without structural control, function may be impaired, unpredictable, or impossible.The search for molecules with a desired function is often achieved by synthesizing a combinatorial library, which contains many or all possible combinations of a set of chemical building blocks (BBs), and then screening this library to identify “successful” structures. The largest libraries made by conventional synthesis are currently of the order of 108 distinct molecules. To put this in context, there are 1013 ways of arranging the 21 proteinogenic amino acids in chains up to 10 units long. Given that we know that a number of these compounds have potent biological activity, it would be highly desirable to be able to search them all to identify leads for new drug molecules. Large libraries of oligonucleotides can be synthesized combinatorially and translated into peptides using systems based on biological replication such as mRNA display, with selected molecules identified by DNA sequencing; but these methods are limited to BBs that are compatible with cellular machinery. In order to search the vast tracts of chemical space beyond nucleic acids and natural peptides, an alternative approach is required.DNA-templated synthesis (DTS) could enable us to meet this challenge. DTS controls chemical product formation by using the specificity of DNA hybridization to bring selected reactants into close proximity, and is capable of the programmed synthesis of many distinct products in the same reaction vessel. By making use of dynamic, programmable DNA processes, it is possible to engineer a system that can translate instructions coded as a sequence of DNA bases into a chemical structure—a process analogous to the action of the ribosome in living organisms but with the potential to create a much more chemically diverse set of products. It is also possible to ensure that each product molecule is tagged with its identifying DNA sequence. Compound libraries synthesized in this way can be exposed to selection against suitable targets, enriching successful molecules. The encoding DNA can then be amplified using the polymerase chain reaction and decoded by DNA sequencing. More importantly, the DNA instruction sequences can be mutated and reused during multiple rounds of amplification, translation, and selection. In other words, DTS could be used as the foundation for a system of synthetic molecular evolution, which could allow us to efficiently search a vast chemical space. This has huge potential to revolutionize materials discovery—imagine being able to evolve molecules for light harvesting, or catalysts for CO2 fixation.The field of DTS ha...

show abstract

Section: Dna-templated Chemistrymentioning

confidence: 99%

The Evolution of DNA-Templated Synthesis as a Tool for Materials Discovery

2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…8a ). Stulz and co-workers 125 have demonstrated that DNA can be employed to template acyl transfer reactions between thioester modified oligonucleotide and a series of amine and thiol based nucleophiles.…”

Section: Molecular Machinesmentioning

confidence: 99%

Exploring chemoselective S-to-N acyl transfer reactions in synthesis and chemical biology

2017

View full text Add to dashboard Cite

S-to-N acyl transfer is a high-yielding chemoselective process for amide bond formation. It is widely utilized by chemists for synthetic applications, including peptide and protein synthesis, chemical modification of proteins, protein-protein ligation and the development of probes and molecular machines. Recent advances in our understanding of S-to-N acyl transfer processes in biology and innovations in methodology for thioester formation and desulfurization, together with an extension of the size of cyclic transition states, have expanded the boundaries of this process well beyond peptide ligation. As the field develops, this chemistry will play a central role in our molecular understanding of Biology.

show abstract

“…This observation can be correlated to the lower pK a of the hydrazide. [94] Using more activated acyl donors (DNA-NHS-ester conjugates; Figure 11.3), nucleic acid-templated amide bond formation has been reported recently in multistep DTS (see also Figure 13). The reaction generally afforded more than 75 % yield within minutes.…”

Section: Templated Hydrolysis and Acyl Transfermentioning

confidence: 92%

Reactions Templated by Nucleic Acids: More Ways to Translate Oligonucleotide‐Based Instructions into Emerging Function

2013

View full text Add to dashboard Cite

The programmability of oligonucleotide recognition offers an attractive platform to direct the assembly of reactive partners that can engage in chemical reactions. Recently, significant progress has been made in both the breadth of chemical transformations and in the functional output of the reaction. Herein we summarize these recent progresses and illustrate their applications to translate oligonucleotide instructions into functional materials and novel architectures (conductive polymers, nanopatterns, novel oligonucleotide junctions); into fluorescent or bioactive molecule using cellular RNA; to interrogate secondary structures or oligonucelic acids; or a synthetic oligomer.

show abstract

Peptidomimetic bond formation by DNA-templated acyl transfer

Cited by 31 publications

References 45 publications

The Evolution of DNA-Templated Synthesis as a Tool for Materials Discovery

The Evolution of DNA-Templated Synthesis as a Tool for Materials Discovery

Exploring chemoselective S-to-N acyl transfer reactions in synthesis and chemical biology

Reactions Templated by Nucleic Acids: More Ways to Translate Oligonucleotide‐Based Instructions into Emerging Function

Contact Info

Product

Resources

About