Presentation 2

Lab Focus: a-Vinylation of Amino Acid Residues and their role as inhibitors for Decarboxylase Enzymes.

	a-Vinyl amino acids have potential application as building blocks for new peptide design, and as inhibitors of amino acid-processing enzymes. For both applications, enantiomerically enriched a-vinyl amino acids are desired. The lab focuses on two complementary approaches that they have undertaken to control the absolute stereochemistry in the synthesis of higher a-vinyl amino acids. Both processes require vinylglycine as a starting molecule.
	The Berkowitz group is currently working on 3 projects:
		Fluorinated Phosphonates
		Podophyllotoxin Etoposide Derivatives
		Novel a-Branched Amino Acids

Vinylation	Vinyl is a common name used to describe an ethylene (ethene) that is attached to another atom/molecule. One example of this is polyvinylchloride (PVC).

	Vinyl functional group. The R-labeled atom on the lower left represents any atom or compound.

Amino Acids	Amino Acids are the building blocks of all proteins. There exist 20 common amino acids and many more less common. All amino acids contain 5 parts; central (alpha) carbon, carboxyl (COOH), amino (NH₂), a hydrogen, and a side chain (R).

	The amino acid Glycine. Glycine contains a lone hydrogen as the side chain. Note the two Hs pointing down from the central carbon.	The amino acid Alanine. Note the Methyl group (-CH₃) pointing down from the central carbon.

Enantiomerism	Enantiomers are molecules who are stereoisomers that are mirror images of one another.

	The R-enantiomeric form of bromochlorofluoromethane	The S-enantiomeric form of bromochlorofluoromethane
	The R refers to a clockwise order of priority from bromine to chlorine to fluorine, whereas the S refers to the counterclockwise order of priority from bromine to chlorine to fluorine. Click here for more.
	The Berkowitz Lab is interested in specific enantiomeric forms of the vinyl amino acids. Enantiomeric forms have properties that are individual to the specific enantiomer, therefore to obtain a specific vinyl amino acid, the stereochemistry becomes essential.

Decarboxylase Enzyme	Decarboxylase enzymes are enzymes that remove a carboxyl group (-COOH) from a substrate. These enzymes usually require the assistance of the the coenzyme Pyridoxal-5-Phosphate (Vitamine B6). The coenzyme aids in weakening the a-carbon-carboxyl carbon bond enabling it to break and stabilize then anion formed by several resonance structures.

	Here is an example of an a-decarboxylation of lysine ( R= -CH2-CH2-CH2-CH2-NH2). The decarboxylase requires pyridoxal-5-phosphate and a hydrogen atom. The reaction involves removing carbon dioxide and adding a hydrogen. The product of an a-decarboxylation of lysine produces 1,5-diaminopentane.
		The coenzyme pyridoxal-5-phosphate (PLP). This coenzyme forms a stable bond between the amino of an amino acid and the carbonyl on the PLP (top carbon on ring- CHO).