9-Fluorenylmethoxycarbonyl (Fmoc) amino acids were first used for solid phase peptide synthesis a little more than a decade ago. Since that time, Fmoc solid phase peptide synthesis methodology has been greatly enhanced by the introduction of a variety of solid supports, linkages, and side chain protecting groups, as well as by increased understanding of solvation conditions. These advances have led to many impressive syntheses, such as those of biologically active and isotopically labeled peptides and small proteins. The great variety of conditions under which Fmoc solid phase peptide synthesis may be carried out represents a truly "orthogonal" scheme, and thus offers many unique opportunities for bioorganic chemistry.

Solid phase peptide synthesis utilizing 9‐fluorenylmethoxycarbonyl amino acids

1. Overview A 2. Protein Redesign B 2.1. Making Use of Native Proteins: Protein Redesign B 2.2. Protein Redesign Based on Functions C 2.2.1. Redesign of Zinc Finger Structural Sites C 2.2.2. Redesign of Zinc Hydrolytic Centers E 2.2.3. Redesign of Heme Centers J 2.2.4. Redesign of Nonheme Redox Centers M 2.2.5. Artificial Metalloenzymes for Regioand Enantioselective Catalysis AA 2.2.6. Redesigned Protein Assemblies as Nanoreactors AK 2.3. Summary AN 3. De Novo Design AN 3.1. A Minimalist Approach: Designing Proteins from Scratch AN 3.2. Interactions between De Novo Designed Peptides and Metal Ions AN 3.2.1. Heavy Metal Toxicity AO 3.2.2. De Novo Designed Metal Centers Based on β-Structures AT 3.2.3. Metal-Induced Protein Folding AV 3.3. De Novo Designed Functional Metalloproteins: The Grail Quest of Protein Design AX 3.3.1. De Novo Designed Hydrolytic Centers AX 3.3.2. De Novo Designed Electron Transfer Centers BB 3.3.3. Other Catalytic Centers BG 3.4. Summary BN 4. Perspective BO Author Information BO Corresponding Author BO Notes BO Biographies BO Abbreviations BR References BR

Protein design: toward functional metalloenzymes.

Advances in methodology in both chemistry and molecular biology allow us to take a fresh look at protein science. Chemical synthesis of peptides and site-directed mutagenesis are now standard research tools, paving the way for the construction of new proteins with tailor-made structural and functional properties. The decisive hurdle on the way lies not in the synthesis of the molecules proper but rather in a better understanding of the complex folding pathways of polypeptide chains into spatially well-defined structures. Can the chemist use his synthetic tools to bypass the notorious “folding problem?” In this article, we present a new approach developed in our laboratory, which opens a chemical route to artificial proteins with predetermined three-dimensional structures, allowing a first step towards the synthesis of new proteins with functional properties.

A Chemical Approach to Protein Design—Template‐Assembled Synthetic Proteins (TASP)

A process for the production of oligomeric or polymeric functional elements from designer elements in which the functional elements are obtainable by the linking of at least two designer elements, at least one of which is itself made up of at least two monomers which are linked by at least one chemical bond which corresponds to the chemical bond between two designer elements.

Process for the evolutive design and synthesis of functional polymers based on designer elements and codes

Heme protein assemblies.

A new general strategy for the construction of artificial proteins with predetermined tertiary structure is presented. Amphiphilic α-helix and β-sheet-forming oligopeptides are assembled on a multifunctional ttemplate molecule which directs the peptide blocks to adopt characteristic folding topologies. The design, synthesis, and conformational properties of these template-assembled synthetic proteins (TASP) are exemplified for βαβ-, α-helix-bundle- and β-barrel-like tertiary structures using specially designed oligopeptides as template molecules. In contrast to linear polypeptide chains of comparable molecular weights, these conceptually novel marcromolecules are readily accessible to chemical synthesis and exhibit excellent solubility in a number of solvents. Experimental evidence is provided for a template-induced intramolecular folding to secondary and tertiary structures in aqueous solutions. This approach opens new prospects for the chemical construction of biomacromolecules with tailormade structural and functional properties.

Hans-Ulrich Gremlich

Papers

The Construction of New Proteins. Part III. Artificial folding units by assembly of amphiphilic secondary structures on a template