Parallel Synthesis Strategy whereby sets of discrete compounds are prepared simultaneously in arrays of physically separate reaction vessels or microcompartments without interchange of intermediates during the assembly process. Contrast Pool/Split.
Partial Library Partly assembled library, or portion thereof, which is reserved to be completed once initial property relationships have been identified. For instance, part of an intermediate pool may not be treated with the final building block until the optimal residue at the final position is known, thus avoiding the need to prepare that pool from the starting materials.
Partial Release Cleavage process designed to release a compound from a solid support in discrete portions, e.g. by using orthogonal linkers or by controlled application of cleavage reagent or condition.
Peptoid Oligomer consisting of repeating N-substituted glycine units.
Peptide A molecule composed of two or more amino acids. Larger peptides are generally referred to as polypeptides or proteins.
Peptide bond Peptide A planar, amide linkage between the amino group of one amino acid and the carboxyl group of another, with the elimination of a molecule of water.
Pharmacokinetics The study of absorption, distribution, matabolism and excretion (ADME) of bioactive compounds in a higher organism.
Pharmacology The science of studying both the mechanisms and the actions of drugs, usually in animal models of disease, to evaluate their potential therapeutic value.
Pharmacophore A pharmacophore is the ensemble of steric and electronic features that is necessary to ensure the optimal supramolecular interactions with a specific biological target structure and to trigger (or to block) its biological response. A pharmacophore does not represent a real molecule or a real association of functional groups, but a purely abstract concept that accounts for the common molecular interaction capacities of a group of compounds towards their target structure.
Phage Display Use of genetically engineered phage to present peptides as segments of their native surface proteins. Peptide libraries may be produced by populations of phage with different gene sequences.
Pharmacophore The ensemble of steric and electronic factors which are necessary to ensure supramolecular interactions with a specific biological target structure.
Phase Switch Strategy for compound isolation, whereby the desired material is rendered sufficiently different from reagents, side-products and other impurities that it may be separated from them by simple physical processes such as filtration or extraction. May be achieved by the attachment of a tag, such as a highly fluorinated component, or other sequestration enabling reagent.
Photolithography Process by which selective masking generates light patterns which direct chemical transformations to certain areas of a photosensitive surface. Coupling of different building blocks to discrete sites may give rise to spatially addressable arrays of compounds.
Pin An elongated device in which the tip acts as a solid support. An array of pins may typically be held such that sets of pins may be simultaneously inserted or retracted from solvents or reagents allowing library preparation by parallel synthesis.
Potency Refers to the concentration of an agent (drug) at which it inhibits an enzyme to a defined extent, i.e. IC50 is the concentration at which an inhibitor blocks the activity of an enzyme 50 per cent.
Point of Diversity Portion of a molecule, or step in a synthetic scheme, where different building blocks may be introduced.
Poly(ethylene glycol) (PEG) Polymer which has been applied both as a soluble support and (as a graft copolymer with a polystyrene matrix) as a linker for combinatorial synthesis. The soluble support may have hydroxyls at both termini, or one or both may be capped or modified with additional functionality.
Pool/Split Strategy for assembly of a combinatorial library. The solid support is divided into portions, each of which is subjected to reaction with a single building block. Pooling of these portions results in a single batch of solid support bearing a mixture of components. Repetition of the divide, couple, recombine processes results in a library where each discrete particle of solid support carries a single library member, and the number of members is equal to the product of the number of building blocks incorporated at each step (i.e. fully combinatorial).
Positional Scan Strategy for identifying individual compounds of interest from a library, whereby a collection of sub-libraries is prepared, equal in number to the total number of building blocks used in the entire library. In each pool, one point of diversity is held constant by incorporating a single building block, while the other positions use all possible building blocks.
Privileged Structure Substructural feature which confers desirable (often drug-like) properties on compounds containing that feature. Often consists of a semi-rigid scaffold which is able to present multiple hydrophobic residues without undergoing hydrophobic collapse.
Property Space Multidimensional representation of a set of compounds in which the axes represent quantifiable properties, such as molecular weight, log P, molar refractivity, etc., and individual compounds are represented by a vector or set of coordinates.
Prodrug A chemical structure that undergoes conversion to an active drug within a biological system, such conversion usually involving metabolism.
Protease An enzyme that hydrolyzes (breaks down a bond and adds water) proteins, especially to peptides.
Protein A molecule composed of a long chain of amino acids. Proteins are the principal constituents of cellular material and serve as enzymes, hormones, structural elements, and antibodies. The molar mass is usually above 100,000.
Protein Kinases Enzymes that phosphorylate certain amino acid residues (most often Ser, Thr, or Tyr) in specific proteins.
