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Biomedical subjects

Steven C Zimmerman

Publications and source records attributed to Steven C Zimmerman.

At least 19 recordsLinked to original sources
PubMed2006

Interplay of fidelity, binding strength, and structure in supramolecular polymers.

In studies of a supramolecular network of polymers formed by self-association of UPy or UG recognition units displayed along a poly(butyl methacrylate) (PBMA) backbone, it was unexpectedly found that the more weakly dimerizing (Kdimer approximately 200 M-1) UG unit produced more assembly than did the very strongly dimerizing UPy unit (Kdimer = 2 x 107 M-1). Likewise, in examining supramolecular blends mediated by the heterocomplexation of DAN and UPy, which occurs upon the mixing of polystyrene containing the DAN unit (PS-DAN) and PBMA-UPy, increasing the mol % of UPy did not produce increased viscosity. 1H NMR showed that both observations can be explained by the intramolecular recognition of UPy. Structural studies show that the length of the chain linking the UPy unit to the backbone is critical, with longer linkers favoring intermolecular dimers. An interplay of linker chain length, polymer Mw, recognition unit mol %, and fidelity determines the extent of network growth.

Journal Article↗
PubMed2006

A supramolecular multi-block copolymer with a high propensity for alternation.

Alternating, multi-block supramolecular copolymers were created using quadruple hydrogen bonding as the noncovalent binding force. One block consisted of two guanosine butyl urea (UG) units attached at the ends of a triethylene glycol linker or a PEG chain (MW = 2 kD). The other block contained a 2,7-diamido-1,8-naphthyridine (DAN) unit at each end of a short alkane diester linker or a 100 kD poly(butyl methacrylate) macromolecule. The UG unit presents an ADDA hydrogen bonding array that is complementary to the DAAD array of DAN, and these form a very strong complex (Kassoc approximately 5 x 107 M-1), whereas UG and DAN weakly self-associate. These recognition properties allowed a multi-block supramolecular polymer to form which exhibits a high propensity for alternation. The self-assembled polymeric structure was shown to be reversibly formed and it was characterized by a combination of dynamic light scattering (DLS), 1H NMR, size exclusion chromatography (SEC), and viscometry.

Journal Article↗
PubMed2006

Formation of a miscible supramolecular polymer blend through self-assembly mediated by a quadruply hydrogen-bonded heterocomplex.

A supramolecular network polymer consisting of a pair of immiscible polymers, poly(butyl)methacrylate (PBMA) and polystyrene (PS), is described. A urea of guanosine (1, UG) and 2,7-diamido-1,8-naphthyridine (2, DAN), which form an exceptionally strong quadruply hydrogen-bonding complex, are displayed at 1-10 mol % along the main backbone of PBMA and PS, respectively. (1)H NMR studies show heterocomplexation between UG and DAN exclusively. This high-fidelity, high-affinity supramolecular connection of two different polymer coils at the molecular level produces a polymer blend. Blends containing different weight ratios of the polymers and mole percent of the recognition units were characterized by AFM and DSC experiments with no isolated domains observed and a single glass-transition temperature (T(g)). The T(g) is tunable by varying the weight ratio of the polymers in the blend. In addition, viscosity measurements, size-exclusion chromatography (SEC), and dynamic light-scattering (DLS) studies demonstrate the formation of a supramolecular network structure.

Journal Article↗
PubMed2006

Higher affinity quadruply hydrogen-bonded complexation with 7-deazaguanine urea.

[structure: see text] UG forms a highly stable quadruply hydrogen-bonded heterocomplex with DAN, but the fidelity of the complex is lowered somewhat by the Hoogsteen-side oligomerization of UG (K(assoc) approximately 230 M(-)(1), CDCl(3)). DeUG was prepared as a more robust analogue of UG lacking the Hoogsteen nitrogen atom. Remarkably, the deaza analogue, DeUG, forms a much more stable complex with DAN (>10-fold higher K(assoc) for DeUG.DAN vs UG.DAN) but also dimerizes more strongly (K(dim) = 880 +/- 40 M(-)(1), CDCl(3)) by adopting a conformation preorganized for both binding and dimerization.

Guanine↗
PubMed2005

A quadruply hydrogen bonded heterocomplex displaying high-fidelity recognition.

An exceptionally strong quadruply hydrogen-bonded complex is formed between 2,7-diamido-1,8-naphthyridine 3 (DAN) and the butylurea of guanosine 6 (UG) in chloroform. The UG unit can be prepared in four steps from guanosine on a 10 g scale in excellent yields without chromatographic purification. The association constant (Kassoc approximately 5 x 10(7) M(-1)) for the UG.DAN complex determined by fluorescence energy transfer from the naphthyridine unit of 3 to coumarin 343 covalently linked UG (18) is among the highest reported for a neutral DNA base-pair analogue. The weak self-association of DAN (Kdimer < 10 M(-1)) and UG (Kdimer ca. 200-300 M(-1)) means that the UG.DAN complex forms with unparalleled fidelity.

Crystallography, X-Ray↗
PubMed2005

Structure-function studies on a synthetic guanosine receptor that simultaneously binds Watson-Crick and Hoogsteen sites.

[structure: see text] A series of receptors (11-16) designed to simultaneously bind the Watson-Crick and Hoogsteen sites of guanosine were synthesized, and their binding of guanosine tri-O-pentanoate (32) was probed via 1H NMR complexation studies in 5% DMSO-d6-chloroform-d. The guanosine receptors were synthesized with aminonaphthalene or aminoquinoline auxiliary groups tethered to N-4 of cytosine via a methylene or carbonyl group. A structure-function relationship was established allowing energetic contributions made by components of nucleoside analogues to be probed and more general design rules formulated that may guide the development of more efficacious DNA bases.

DNA↗
PubMed2005

Synthesis and characterization of an electroactive surface that releases gamma-aminobutyric acid (GABA).

We report the synthesis and characterization of a new electroactive surface capable of releasing the neurotransmitter gamma-aminobutyric acid (GABA) upon reduction. The GABA was anchored to an alkanethiol via electrochemically active quinone (abbreviation, TM-GABA). The quinone unit, upon reduction to the hydroquinone, cyclizes to release GABA into solution. The half-life is 99 s. The self-assembled monolayer (SAM) of TM-GABA on gold was prepared and characterized with several surface sensitive techniques. X-ray photoelectron spectroscopy (XPS) explored the SAM formation of TM-GABA on Au surfaces. Cyclic voltammograms showed the ability to electrochemically control the quinone unit at the distal end of the chain. GABA was selectively released upon electrochemical reduction at a potential of -700 mV. The functional GABA terminal group was detected by surface plasmon resonance measurements of anti-GABA antibody binding.

Biocompatible Materials↗
PubMed2005

Synthesis of a soluble ureido-naphthyridine oligomer that self-associates via eight contiguous hydrogen bonds.

[structure; see text] An iterative synthetic route to organic-soluble ureido-naphthyridine oligomers has been developed. Use of this protocol allowed synthesis of a short ureido-naphthyridine oligomer, which presents a self-complementary DDAADDAA hydrogen bonding array (D = hydrogen bond donor, A = hydrogen bond acceptor). Strong self-association via eight hydrogen bonds was observed in organic solution.

Hydrogen Bonding↗
PubMed2005

A highly stable quadruply hydrogen-bonded heterocomplex useful for supramolecular polymer blends.

The butyl urea of guanosine (UG) presents an ADDA hydrogen-bonding array that is complementary to the DAAD array of 2,7-diamido-1,8-naphthyridine (DAN). The stability of the DAN.UG complex was measured by fluorimetry using the fluorescence resonance energy transfer (FRET) from the naphthyridine ring to a coumarin 343 moiety linked covalently to the UG unit. The quadruply hydrogen-bonded complex is extremely stable with a measured association constant, Kassoc, of 3 x 108 M-1. Unlike related hydrogen-bonding modules, the guanosine urea, UG, contains a relatively fixed tautomeric form and only weakly self-associates (Kdimer = ca. 200 M-1). The DAN unit was linked to a styrene-based monomer and copolymerized with styrene to form a polymer (PS-DAN) containing a controlled number of the DAAD recognition units. Likewise, a methacrylate monomer containing the UG unit was copolymerized with butyl methacrylate to form a polymer (PBMA-UG). Blends formed from PS-DAN and PBMA-UG were characterized by DSC, SEC, and viscometry. The importance of selective heterocomplexation and weak self-association in forming the blended networks was demonstrated by using a ureidopyrimidinone (UPy) unit, which also forms strong heterocomplexes with DAN but is able to strongly self-associate.

Journal Article↗
PubMed2004

On the nature of dendrimer cross-linking by ring-closing metathesis.

The ring-closing metathesis (RCM) mediated cross-linking of dendrimer 1 and it subunits was examined. Through the combined use of MALDI-MS-TOF, SEC, NMR, and X-ray crystallographic analysis it was shown that the cross-links are formed with the following order of preference: type d >/= type c > type b > type a.

Cross-Linking Reagents↗
PubMed2004

Cross-linking dendrimers with allyl ether end-groups using the ring-closing metathesis reaction.

A third generation Frechet-type dendrimer containing 24 allyl ether end-groups was synthesized, cross-linked using the ring-closing metathesis (RCM) reaction, and the core was removed hydrolytically without significant fragmentation. The results are analogous to those previously reported for homoallyl ether dendrimers (Wendland, M. S.; Zimmerman, S. C. J. Am. Chem. Soc. 1999, 121, 1389-1390) suggesting that the less readily available homoallyl ether dendrimers can be replaced by their allyl ethers analogues in a range of applications.

Allyl Compounds↗
PubMed2004

Organic nanoparticles whose size and rigidity are finely tuned by cross-linking the end groups of dendrimers.

Dendrimers with molecular weights ranging from ca. 2700 to 11 000 and from 16 to 64 homoallyl ether end groups were cross-linked using the Grubbs ring-closing metathesis reaction. A combination of SEC, MALDI-TOF-MS, and AFM were used to characterize the cross-linked nanoparticles. The data suggest a significant decrease in volume with cross-linking and a concomitant increase in rigidity, both of which can be controlled independently with a fair degree of precision.

Cross-Linking Reagents↗
PubMed2004

Synthesis and duplex DNA recognition studies of oligonucleotides containing a ureido isoindolin-1-one homo-N-nucleoside. A comparison of host-guest and DNA recognition studies.

In an effort to construct non-natural bases to be used in triplex-based antigene DNA recognition strategies, a uriedo-isoindolin-1-one homo-N-nucleoside base was designed to bind the cytosine-guanine (CG) base pair. An organic soluble analogue of this base was shown to effectively complex CG (K(assoc)=740M(-1)) in chloroform through formation of three hydrogen bonds (Mertz, E.; Mattei, S.; Zimmerman, S. C. Org. Lett. 2000, 2, 2931-2934). The novel nucleoside base was synthesized and successfully incorporated into oligonucleotides which were used in triple helix melting temperature studies. Low melting temperatures were observed when the isoindolin-1-one base was paired opposite CG as well as GC, TA, and AT, thus indicating that despite favorable recognition in model studies, the artificial base did not effectively recognize duplex DNA to form pyrimidine-purine-pyrimidine type triple helices.

Cytosine↗
PubMed2003

Molecular imprinting inside dendrimers.

Synthetic hosts capable of binding porphyrins have been produced by a mixed-covalent-noncovalent imprinting process wherein a single binding site is created within cross-linked dendrimers. Two synthetic hosts were prepared, using as templates 5,10,15,20-tetrakis(4-hydroxyphenyl)porphyrin and 5,10,15,20-tetrakis(3,5-dihydroxyphenyl)porphyrin. These two templates were esterified with, respectively, fourth- and third-generation Fréchet-type dendrons containing homoallyl end-groups. The resulting tetra- and octadendron macromolecules underwent the ring-closing metathesis reaction using Grubbs' Type I catalyst, RuCl(2)(P(C(6)H(5))(3))(2)(CHCH(2)C(6)H(5)), to give extensive interdendron cross-linking. Hydrolytic removal of the porphyrin cores afforded imprinted hosts whose ability to bind porphyrins with various peripheral substituents was investigated by UV-visible spectrophotometric titrations and size exclusion chromatography. The results indicate a high yield of imprinted sites that show high selectivity for binding of porphyrins capable of making at least four hydrogen bonds, but only a moderate degree of shape selectivity.

Binding Sites↗
PubMed2003

Kinetics and thermodynamics of amine and diamine signaling by a trifluoroacetyl azobenzene reporter group.

[reaction: see text] (Trifluoroacetyl)azobenzene dyes were previously employed as amine reporter groups (chemosensors) in a dendrimer-based monomolecular imprinting system. Kinetic and binding studies with a range of amines and diamines show that the highly selective signaling observed for alkane diamines by these imprinted dendrimers arises from a kinetic effect due to intramolecular general base-catalyzed carbinolamine formation with the dye itself. The relationship between diamine structure and carbinolamine stability and rate of formation is described.

Amines↗
PubMed2003

Synthetic hosts via molecular imprinting--are universal synthetic antibodies realistically possible?

Of the many ways to make synthetic hosts, one of the most appealing involves molecular imprinting. In the commonest approach monomer units assemble around or are attached to a template (imprint) molecule and then linked together using a cross-linking agent. Template removal ideally leaves cavities within the molecularly imprinted polymer (MIP) that possess a shape and functional group complementarity to the imprint molecule allowing its tight and selective uptake. This review highlights some recent advances in the synthesis of MIPs (often called "synthetic antibodies") and enumerates a "wish list" of properties for the perfect MIP that may guide future studies.

Antibodies↗