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By E. J. Corey

Molecules and medication presents, for the 1st time ever, a very built-in examine chemistry, biology, drug discovery, and medication. It delves into the invention, program, and mode of motion of a couple of hundred of the main major molecules in use in sleek drugs. beginning sections of the e-book supply a distinct, transparent, and concise advent, which allows readers to appreciate chemical formulation.

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Jr. • . ~ &;,.. ,~ : ... JI':' .. Z' • .. J ". '. ;~ . . . ~ " .. '"lI·~ (. . , ,,~ . • l ". ' • ) MOLECULES AND MEDICINE PROTEINS AND THREE·DIMENSIONAL PROTEIN STRUCTURES Introduction Proteins are very large molecules formed by the joining of many a-amino acid subunits through amide linkages. A subsection of a protein chain can be represented in a general­ and highly simplified way by a two­ dimensional line drawing (Figure 1). ~yt~~~yt~~~) .. R' 0 R' 0 R' Figure 1. Portion of a protein/polypeptide chain .

32 A). ~J ~ o oe l OH H2N ~ N ~ ~ / H2N ~ N0~~OH H, N - 0 Ala-Gly-Phe (alanyl-glycinyl-phenylalanine) 0 y glycylglycine R Figure 9. Structures of a generic tripeptide and of the specific tripeptide Ala-Gly-Phe. 32 A efr", : , ,.. 46 A (free rotation) (free rotation) The sequence of the individual amino acids in a polypeptide or protein, the primary structure, is critical to its preferred three­ dimensional shape and properties. It is the very large number of possible sequences that enables the existence of an unima~inably large number of possible proteins (100 0 for a 100 amino acid protein).

2005, 353, 1711-1723; 2. Br. J. Pharmacal. 2006 , 148, 245-254 ; 3. Ann. N. Y. Acad. Sci. 2006, 1088, 396-409; Refs. p. 81 45 ~ MOLECULES AND MEDICINE METHOTREXATE (TREXALLm) Structural Formula Ball-and-Stick Model Space-filling Model i HJ ~ N~" H N" 0 :~"'rOH h N, H'"hIN 0LOH. I N-y-N NH, • = Carbon = Hydrogen • = Oxygen • = Nitrogen Year of discovery: 1948 (Lederle); Year of introduction : 1953; Drug category: Antimeta­ bolite/disease-modifying anti-inflammatory agenUimmunosuppressant; Main uses: For treatment of inflammation associated with autoimmunity (rheumatoid arthritis, Crohn's disease and psoriasis) ; Other brand names: Rheumatrex; Re/ated drugs: Trimetrexate (Neutrexin) , Pemetrexed (Alimta).

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