PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins

Farrera-Soler, Lluc; Daguer, Jean‐Pierre; Raunft, Patrick; Barluenga, Sofía; Winssinger, Nicolas

doi:10.1016/j.bmc.2020.115458

Cited by 15 publications

(11 citation statements)

References 66 publications

(60 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 47 More recently, this approach of supramolecular dynamic assembly has been developed into a library format, called a PNA-based dynamic combinatorial library (PDCL) with >6000 assemblies. 46 The PDCL is synthesized in a “split-and-mix” fashion wherein the PNA, linker, and glycan were conjugated step-wise as three BBs in a combinatorial library. The library contains not only the structural diversity, but also the positional diversity of the glycan ligands.…”

Section: Development Of Dedlsmentioning

confidence: 99%

“…With the rapid development of DEL-compatible chemistry, arguably, the chemical space of DELs is limited by the availability of the building blocks, rather than the reactions to connect them. 2,7 Recent innovations have also integrated DEL with many legacy and emerging techniques, such as fragment-based drug discovery (FBDD), 32,[37][38][39][40] the dynamic combinatorial library (DCL), [41][42][43][44][45][46][47] diversity-oriented synthesis (DOS), 48,49 machine learning, [50][51][52] OBOC libraries/microfluidics, 24,26,[53][54][55] flow cytometry, 23,27,28 etc., leading to novel applications in ligand discovery and functional assays. 9,30 DEL selections have generated a number of clinical candidates, 17 such as GSK2256294, an epoxide hydrolase inhibitor to treat pulmonary disease, 17,18 GSK2982772, a first-in-class receptor-interacting protein-1 kinase inhibitor to treat inflammatory diseases, 17,19 and X-165, an autotaxin inhibitor as the clinical candidate for pulmonary fibrosis.…”

Section: Dna-encoded Chemical Library (Del)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Recent advances in DNA-encoded dynamic libraries

Shi

Zhou

2022

RSC Chem. Biol.

View full text Add to dashboard Cite

show abstract

Section: Development Of Dedlsmentioning

confidence: 99%

Section: Dna-encoded Chemical Library (Del)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Recent advances in DNA-encoded dynamic libraries

Shi

Zhou

2022

RSC Chem. Biol.

View full text Add to dashboard Cite

show abstract

“…The ESAC library developed by the Neri group is an elegant approach to accessing high-quality dual-pharmacophore DELs. , The Hamilton group showed that proteins could template the dynamic hybridization of DNA-displayed ligands . The integration of these two concepts was lately elaborated into several types of DNA-encoded dynamic libraries (DEDLs) by Zhang, , Winssinger, and us. ,, DEDLs contain short complementary DNA strands (six to seven bases) so that the DNA duplexes are dynamic under physiological conditions (Figure a). Target addition promotes the formation of high-affinity duplexes, and a comparison of the equilibria before and after target addition identifies the binder pairs.…”

Section: Dna-encoded Dynamic Librarymentioning

confidence: 99%

“…Finally, it is worth noting that DEDL selections are not limited to the solution phase. The dynamic nature of DEDLs suggests that on-bead selections may be difficult since the washes will almost inevitably disrupt the equilibrium; however, it has been successfully demonstrated with multivalent systems of high binding affinities , or using a thermal reshuffling strategy to stabilize the duplexes …”

Section: Dna-encoded Dynamic Librarymentioning

confidence: 99%

Evolution of the Selection Methods of DNA-Encoded Chemical Libraries

Song

2021

Acc. Chem. Res.

View full text Add to dashboard Cite

Metrics & MoreArticle Recommendations * sı Supporting Information CONSPECTUS: In the past two decades, a DNA-encoded chemical library (DEL or DECL) has emerged and has become a major technology platform for ligand discovery in drug discovery as well as in chemical biology research. Although based on a simple concept, i.e., encoding each compound with a unique DNA tag in a combinatorial chemical library, DEL has been proven to be a powerful tool for interrogating biological targets by accessing vast chemical space at a fraction of the cost of traditional high-throughput screening (HTS). Moreover, the recent technological advances and rapid developments of DEL-compatible reactions have greatly enhanced the chemical diversity of DELs. Today, DELs have been adopted by nearly all major pharmaceutical companies and are also gaining momentum in academia. However, this field is heavily biased toward library encoding and synthesis, and an underexplored aspect of DEL research is the selection methods. Generally, DEL selection is considered to be a massive binding assay conducted over an immobilized protein to identify the physical binders using the typical bind−wash−elute procedure. In recent years, we and other research groups have developed new approaches that can perform DEL selections in the solution phase, which has enabled the selection against complex biological targets beyond purified proteins. On the one hand, these methods have significantly widened the target scope of DELs; on the other hand, they have enabled the functional and potentially phenotypic assays of DELs beyond simple binding. An overview of these methods is provided in this Account.Our laboratory has been using DNA-programmed affinity labeling (DPAL) as the main strategy to develop new DEL selection methods. DPAL is based on DNA-templated synthesis; by using a known ligand to guide the target binding, DPAL is able to specifically establish a stable linkage between the target protein and the ligand. The DNA tag of the target-ligand conjugates serves as a programmable handle for protein characterization or hit compound decoding in the case of DEL selections. DPAL also takes advantage of the fast reaction kinetics of photo-cross-linking to achieve high labeling specificity and fidelity, especially in the selection of DNA-encoded dynamic libraries (DEDLs). DPAL has enabled DEL selections not only in buffer and cell lysates but also with complex biological systems, such as large protein complexes and live cells. Moreover, this strategy has also been employed in other biological applications, such as site-specific protein labeling, protein detection, protein profiling, and target identification. In the Account, we describe these methods, highlight their underlying principles, and conclude with perspectives of the development of the DEL technology.

show abstract

Glyco‐DNA: Enzymatic Synthesis of Base‐Modified and Hypermodified DNA Displaying up to Four Different Monosaccharide Units in the Major Groove

Krömer,

Poštová Slavětínská,

Hocek

2024

Chemistry A European J

View full text Add to dashboard Cite

A portfolio of six modified 2'‐deoxyribonucleoside triphosphate (dNTP) derivatives derived from 5‐substituted pyrimidine or 7‐substituted 7‐deazapurine bearing different carbohydrate units (d‐glucose, d‐galactose, d‐mannose, l‐fucose, sialic acid and N‐Ac‐d‐galactosamine) tethered through propargyl‐glycoside linker was designed and synthesized via the Sonogashira reactions of halogenated dNTPs with the corresponding propargyl‐glycosides. The nucleotides were found to be good substrates for DNA polymerases in enzymatic primer extension and PCR synthesis of modified and hypermodified DNA displaying up to four different sugars. Proof of concept binding study of sugar‐modified oligonucleotides with concanavalin A showed positive effect of avidity and sugar units count.

show abstract

PNA-Based Dynamic Combinatorial Libraries (PDCL) and screening of lectins

Cited by 15 publications

References 66 publications

Recent advances in DNA-encoded dynamic libraries

Recent advances in DNA-encoded dynamic libraries

Evolution of the Selection Methods of DNA-Encoded Chemical Libraries

Glyco‐DNA: Enzymatic Synthesis of Base‐Modified and Hypermodified DNA Displaying up to Four Different Monosaccharide Units in the Major Groove

Contact Info

Product

Resources

About