text: Encoded Self-Assembling Chemical (ESAC) libraries rely on the principle that two sublibraries of a size of x members (e.g. 10) containing a constant complementary hybridization domain can yield a combinatorial DNA-duplex library after hybridization with a complexity of x uniformly represented library members (e.g. 10). Each sub-library member would consist of an oligonucleotide containing a variable, coding region flanked by a constant DNA sequence, carrying a suitable chemical modification at the oligonucleotide extremity. The ESAC sublibraries can be used in at least four different embodiments.
  * A sub-library can be paired with a complementary oligonucleotide and used as a DNA encoded library displaying a single covalently linked compound for affinity-based selection experiments.
  * A sub-library can be paired with an oligonucleotide displaying a known binder to the target, thus enabling affinity maturation strategies.
  * Two individual sublibraries can be assembled combinatorially and used for the de novo identification of bindentate binding molecules.
  * Three different sublibraries can be assembled to form a combinatorial triplex library.
  Preferential binders isolated from an affinity-based selection can be PCR-amplified and decoded on complementary oligonucleotide microarrays or by concatenation of the codes, subcloning and sequencing. The individual building blocks can eventually be conjugated using suitable linkers to yield a drug-like high-affinity compound. The characteristics of the linker (e.g. length, flexibility, geometry, chemical nature and solubility) influence the binding affinity and the chemical properties of the resulting binder.(Fig.3)
  Bio-panning experiments on HSA of a 600-member ESAC library allowed the isolation of the 4-(p-iodophenyl)butanoic moiety. The compound represents the core structure of a series of portable albumin binding molecules and of Albufluor a recently developed fluorescein angiographic contrast agent currently under clinical evaluation.
  ESAC technology has been used for the isolation of potent inhibitors of bovine trypsin  and for the identification of novel inhibitors of stromelysin-1 (MMP-3), a matrix metalloproteinase involved in both physiological and pathological tissue remodeling processes, as well as in disease processes, such as arthritis and metastasis.