Journal article Open Access

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

Lluc Farrera-Soler; Jean-Pierre Daguer; Patrick Raunft; Anne Imberty; Sofia Barluenga; Nicolas Winssinger

Selection from dynamic combinatorial libraries (DCL) benefit from the dynamic nature of the library that can change constitution upon addition of a selection pressure, such as ligands binding to a protein. This technology has been predominantly used with small molecules interacting with each other through reversible covalent interaction. However, application of this technology in biomedical research and drug discovery has been limited by the reversibility of covalent exchange and the analytical deconvolution of small molecule fragments.   Here we report a supramolecular approach based on the use of a constant short PNA tag to direct the combinatorial pairing of fragment.  This PNA tag yields fast exchange kinetics, while still delivering the benefits of cooperativity, and provides favourable properties for analytical deconvolution by MALDI.  A selection of > 6 000 assemblies of glycans (mono-, di-, tri-saccharides) targeting AFL, a lectin from pathogenic fungus, yielded a 95 nM assembly, nearly three orders of magnitude better affinity than the corresponding glycan alone (41 µM).

Files (108.4 MB)
Name Size
Biotinyation RSL.txt
md5:65e3a5898c951336158d9f756a2625e4
2.1 MB Download
Biotinylation AFL.txt
md5:4a49fe5d271fd5d2fbcbcf4d8af4d1f9
6.2 MB Download
Full library starting library.txt
md5:309f85b044eb59b12c469c5f979dfc69
257.7 kB Download
Full selection RSL part 1.txt
md5:5bfc920f17e57f94813c73f167157332
35.5 kB Download
Full selection RSL part 2.txt
md5:e75ef69ff885e7ff4e9b7fb5b3d3cd91
32.5 kB Download
Full selection RSL part 3.txt
md5:a268369fc6bf9d13a61d64355874b495
32.1 kB Download
Full selection RSL part 4.txt
md5:03a86419c5bdd07fa33608136061a4e3
31.2 kB Download
FUll selection RSL part 5
md5:643bffd7f59523203aac4d904e0f596d
14.7 kB Download
M0A.txt
md5:fb5429a0e7f0e356b83f043b5333900e
2.9 MB Download
MKA.txt
md5:44a29efaaea8dd6f46b68563f5523bc7
2.7 MB Download
MXA.txt
md5:c32405232594792dfb53b903ba189a23
1.8 MB Download
N0A.txt
md5:cd9f753bedebe00dc0201e3e4c5c5c8f
2.5 MB Download
NKA.txt
md5:74f425dc2971a7300234eeea7540b914
2.7 MB Download
No protein fucose glucose 1 to 1.txt
md5:a1a477d6f77304c31679232810595094
38.8 kB Download
no protein fucose glucose 1 to 99.txt
md5:a1a477d6f77304c31679232810595094
38.8 kB Download
NXA.txt
md5:c32405232594792dfb53b903ba189a23
1.8 MB Download
RSL selection big library 60C.txt
md5:972757b1915dbb2981a92c13670027c9
111.6 kB Download
Selection AFL rt.txt
md5:9c169a1fb85e5e2e91d85d88f5770439
198.1 kB Download
Selection full library RSL rt.txt
md5:65e441ff2ff50b0e99e6d015243d548a
237.6 kB Download
Selection RSL 1 to 1.txt
md5:c87f40653c65da8944e9c32986677e29
37.9 kB Download
Selection RSL fucose glucose 1 to 99.txt
md5:0c20b1e69f06ef9e02972469425be9be
37.9 kB Download
Single sequence Fucose.txt
md5:4fdc04c7fe9dbce8129897590a16075e
2.3 MB Download
Single sequence glucose.txt
md5:b749a80ad2ade6f96cd93ffd48c61656
3.0 MB Download
SPR_AFL_2fucosyllactose_alone
md5:ef1f98bf35b465052a486e457a5b31a6
706.6 kB Download
SPR_AFL_Hits
md5:7f2dddd4d19837515ca1ee90ded56484
29.6 MB Download
SPR_MOA_MXA_MKA_alone_with_AFL
md5:14d44520c438c3bba418bd0879ff1aa7
7.9 MB Download
SPR_MOA_MXA_MKA_alone_with_RSL
md5:0bf8dcb5eeb9a0a506b08852bc3ff5a0
7.9 MB Download
SPR_RSL_2fucosyllactosealone
md5:7bf060fe85964dd439655fe79e63b284
755.2 kB Download
SPR_RSL_Hits
md5:de51afbe1e6f744b1fa253484e0222fe
29.6 MB Download
starting lib 2fucosyllactose.txt
md5:300ccaac44f56a11ee12c061c6e600ce
290.6 kB Download
Starting lib cellobiose.txt
md5:829b5f479c0cecd04a421293bdf9b13f
297.6 kB Download
Starting lib GalSPhe.txt
md5:7710727b43e0ca103eeb956d3e29783c
284.4 kB Download
Starting lib GlcNAc cluster.txt
md5:8bf2879303d88f5877c4138d38d68691
256.4 kB Download
Starting lib glucose.txt
md5:0da16ce3d8b25db246ed151e0e55e3c2
299.1 kB Download
Starting lib glucoseamine.txt
md5:e804f1d226b08d9a5f11555a42a49ca9
204.6 kB Download
Starting lib GluNAc.txt
md5:c7d1cd8afd5dfd48a122edb7f1cd9edb
294.7 kB Download
Starting lib Maltose.txt
md5:258534aacdb663fe451545c7b688044f
295.4 kB Download
Starting lib Mannose.txt
md5:291796dc462826fe69d9e490afd58121
279.8 kB Download
Starting lib xylose.txt
md5:52a8e81293ad5f2e6fed104b627092fb
285.3 kB Download
Starting library 1 to 1 fucose glucose.txt
md5:b77c7ac652eaf04fffc3cc8c42bc351b
45.5 kB Download
Starting library fucose glucose 1 to 99.txt
md5:577e0a1d276f806a362e75e88df84727
37.2 kB Download
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