Rational Design of Bioorganometallic Foldamers: A Potential Model for Parallel β‐Helical Peptides

Chowdhury, Somenath; Schatte, Gabriele; Kraatz, Heinz‐Bernhard

doi:10.1002/ange.200602248

Cited by 26 publications

(13 citation statements)

References 48 publications

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“…This Aufbau principle with two cooperative hydrogen bonds [nine-and 11-membered rings; (P)-1,2 0 oriented ferrocene] has been elegantly implemented in foldamers consisting of [Ala-Fca] units (e.g., tBuO-CO-(Ala-Fca) 3 -OMe; K; Scheme 21.2) by Kraatz et al, thus underlining the high stability of this motif [22]. Unfortunately, however, no DFTstudy on such large oligoferrocenes with alternating Ala and Fca units has yet been reported.…”

Section: Simple Ferrocene Amino Acid (Bio)conjugatesmentioning

confidence: 99%

Elucidation of the Conformational Freedom of Ferrocene Amino Acid (Bio)Conjugates: A Complementary Theoretical and Experimental Approach

Heinze

Hüttinger

Siebler

2011

Modeling of Molecular Properties

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Introduction1-Amino-1 0 -carboxyferrocene H-Fca-OH [1-4] (Scheme 21.1) is a versatile starting material for the preparation of 1,n 0 disubstituted ferrocenes with distinguished and unique properties. By placing the hydrogen atom donor and hydrogen atom acceptor sites in the different strands of 1,n 0 disubstituted ferrocene derivatives, interstrand hydrogen bonds are feasible giving ansa-ferrocenes. For example, an interstrand hydrogen bond has been observed in Me-CO-Fca-OBt (Bt ¼ 1-benzotriazole) with the triazole heterocycle acting as hydrogen atom acceptor and the NH group acting as hydrogen atom donor, giving an eight-membered ring, excluding the iron center ( Figure 21.1a) [4]. In contrast, the N-acyl urea derivative Me-CO-Fca-NCy-CO-NHCy (Cy ¼ cyclohexyl) features a more strained six-membered ring with the Fca carbonyl unit CO Fca being the acceptor, although larger ring motifs are also possible -for example, an eight-membered ring with the ureylene carbonyl CO ureylene as acceptor and a 10-membered ring with the acetyl carbonyl CO Ac as acceptor and the NH ureylene as donor (Figure 21.1b) [4].In cases where there are several acceptor and donor sites in the two arms, many ring motifs become possible. This holds especially true for peptidic Fca conjugates with organic amino acids or with further Fca units as arms, with each additional amide group providing both a potential hydrogen acceptor and donor site. In natural peptides built from a-amino acids, both intramolecular and intermolecular hydrogen bonds allow the formation of a-helices, b-sheets, or turns. In conjugates incorporating 1,n 0 ferrocene units, a very flexible hinge is introduced into the backbone which allows for small and large hydrogen-bonded ring systems. The two strands can be oriented approximately in the same direction (v ¼ 0 AE 36 ; 1,1 0 rotational isomer), rotated clockwise by 360 /5 ¼ 72 (v ¼ 72 AE 36 ; 1,2 0 rotational isomer), rotated clockwise by 2 Â 360 /5 ¼ 144 (v ¼ 144 AE 36 ; 1,3 0 rotational isomer), rotated anticlockwise by À2 Â 360 /5 ¼À 144 (v ¼À 144 AE 36 ; 1,4 0 rotational isomer), or rotated anticlockwise by À360 /5 ¼À 72 (v ¼À 72 AE 36 ; 1,5 0 rotational isomer).

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Section: Simple Ferrocene Amino Acid (Bio)conjugatesmentioning

confidence: 99%

Elucidation of the Conformational Freedom of Ferrocene Amino Acid (Bio)Conjugates: A Complementary Theoretical and Experimental Approach

Heinze

Hüttinger

Siebler

2011

Modeling of Molecular Properties

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“…Other research into this area has focused on the attachment of the peptides to the cyclopentadienyl core to generate either ‘parallel’ or ‘anti-parallel’ strands (Barisic et al 2004; Chowdhury et al 2005). The most recent report from the Kraatz group detailed the generation of β-helices (Chowdhury et al 2006) and these efforts have now been extended to β-sheets. In addition, unlike some previous reports using both covalent and non-covalent coordination methods, researchers have now been able to maintain the β-sheet conformation beyond two residues, demonstrating a more complete β-sheet.…”

Section: Turn Structuresmentioning

confidence: 99%

Synthetic mimetics of protein secondary structure domains

Ross

Katt

Hamilton

2010

Phil. Trans. R. Soc. A.

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Proteins modulate the majority of all biological functions and are primarily composed of highly organized secondary structural elements such as helices, turns and sheets. Many of these functions are affected by a small number of key protein–protein contacts, often involving one or more of these well-defined structural elements. Given the ubiquitous nature of these protein recognition domains, their mimicry by peptidic and non-peptidic scaffolds has become a major focus of contemporary research. This review examines several key advances in secondary structure mimicry over the past several years, particularly focusing upon scaffolds that show not only promising projection of functional groups, but also a proven effect in biological systems.

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“…[15][16][17][18][19][20] Foldamers composed of the repeating unit [Fca-Ala] were prepared and characterized by Kraatz et al (Ala = alanine). [21] However, electronic communication between the ferrocene units in these alternating peptides was neither reported nor expected. [21] Kraatz and Mahmoud described a symmetrical trinuclear ferrocene Fn(NHCO-Fn-COOMe) 2 Abstract: Trinuclear ferrocene trisamides were synthesized from an Fmoc-or Boc-protected ferrocene amino acid, and hydrogen-bonded zigzag conformations were determined by NMR spectroscopy, molecular modelling, and X-ray diffraction.…”

Section: Introductionmentioning

confidence: 96%

“…[21] However, electronic communication between the ferrocene units in these alternating peptides was neither reported nor expected. [21] Kraatz and Mahmoud described a symmetrical trinuclear ferrocene Fn(NHCO-Fn-COOMe) 2 Abstract: Trinuclear ferrocene trisamides were synthesized from an Fmoc-or Boc-protected ferrocene amino acid, and hydrogen-bonded zigzag conformations were determined by NMR spectroscopy, molecular modelling, and X-ray diffraction. In these ordered secondary structures orientation of the individual amide dipole moments approximately in the same direction results in a macrodipole moment similar to that of a-helices composed of a-amino acids.…”

Section: Introductionmentioning

confidence: 96%

Oligonuclear Ferrocene Amides: Mixed‐Valent Peptides and Potential Redox‐Switchable Foldamers

Siebler

Linseis

Gasi

et al. 2011

Chemistry A European J

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Trinuclear ferrocene tris-amides were synthesized from an Fmoc- or Boc-protected ferrocene amino acid, and hydrogen-bonded zigzag conformations were determined by NMR spectroscopy, molecular modelling, and X-ray diffraction. In these ordered secondary structures orientation of the individual amide dipole moments approximately in the same direction results in a macrodipole moment similar to that of α-helices composed of α-amino acids. Unlike ordinary α-amino acids, the building blocks in these ferrocene amides with defined secondary structure can be sequentially oxidized to mono-, di-, and trications. Singly and doubly charged mixed-valent cations were probed experimentally by Vis/NIR, paramagnetic ¹H NMR and Mössbauer spectroscopy and investigated theoretically by DFT calculations. According to the appearance of intervalence charge transfer (IVCT) bands in solution, the ferrocene/ferrocenium amides are described as Robin-Day class II mixed-valent systems. Mössbauer spectroscopy indicates trapped valences in the solid state. The secondary structure of trinuclear ferrocene tris-amides remains intact (coiled form) upon oxidation to mono- and dications according to DFT calculations, while oxidation to the trication should break the intramolecular hydrogen bonding and unfold the ferrocene peptide (uncoiled form).

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Rational Design of Bioorganometallic Foldamers: A Potential Model for Parallel β‐Helical Peptides

Cited by 26 publications

References 48 publications

Elucidation of the Conformational Freedom of Ferrocene Amino Acid (Bio)Conjugates: A Complementary Theoretical and Experimental Approach

Elucidation of the Conformational Freedom of Ferrocene Amino Acid (Bio)Conjugates: A Complementary Theoretical and Experimental Approach

Synthetic mimetics of protein secondary structure domains

Oligonuclear Ferrocene Amides: Mixed‐Valent Peptides and Potential Redox‐Switchable Foldamers

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