A Wireframe DNA Cube ‐ Antibody Conjugate for Targeted Delivery of Multiple Copies of Monomethyl Auristatin E

2021 ◽  
Author(s):  
Kurt Vesterager Gothelf ◽  
Anders Märcher ◽  
Minke Anne Door Nijenhuis
Keyword(s):  
Targeted Delivery ◽  
Multiple Copies ◽  
Antibody Conjugate

Alkaline Dissociation Products of Lumbricus Terrestris Hemoglobin Viewed with the STEM

1981 ◽  
Vol 39 ◽  
pp. 434-435
Author(s):  
O. H. Kapp ◽  
M. Ohtsuki ◽  
N. Robin ◽  
S. N. Vinogradov ◽  
A. V. Crewe
Keyword(s):  
Carbon Film ◽  
Lumbricus Terrestris ◽  
Uranyl Acetate ◽  
Acetate Solution ◽  
Oxygen Carriers ◽  
Complex Molecules ◽  
Thin Carbon ◽  
Thin Carbon Film ◽  
Multiple Copies ◽  
Hill Coefficients

Annelid extracellular hemoglobins are among the largest known proteins (M.W = 3.9 x 106), and together with the hemocyanins are the largest known oxygen carriers. They display oxygen affinities generally higher than those o vertebrate hemoglobins with Hill coefficients ranging from slightly higher than unity to values as high as 5-6. These complex molecules are composed of multiple copies of as many as six different polypeptides and posse: approximately 150 hemes per molecule.The samples were diluted to 100-200 μg/ml with distilled water just before application to a thin carbon film (∽15 Å thick). One percent (w/v) uranyl acetate solution was used for negative staining for 2 minutes and dried in air. The specimens were examined with the high resolution STEM. Their general appearance is that of a hexagonal bilayer (Fig. 1), each layer consisting of six spheroidal subunits. The corner to corner hexagonal dimensic is approximately 300 Å and the bilayer thickness approximately 200 Å.

pH Dependent Release Potential of Natural Polymers in Sustained Release of Ornidazole From Colon Targeted Delivery System)

2019 ◽  
Vol 9 (02) ◽  
Author(s):  
Sharma Pankaj ◽  
Tailang Mukul
Keyword(s):  
Drug Release ◽  
Delivery System ◽  
Targeted Delivery ◽  
Guar Gum ◽  
Acidic Environment ◽  
Natural Polymers ◽  
Weight Variation ◽  
Curve Determination ◽  
Preformulation Studies

The aim of present work was to prepare colon specific delivery system of Ornidazole using different ratio of shellac, zein and guar gum. From study of various literature it revealed that shellac, zein and guar gum released drug from dosage form at the pH of 6.9, 11.5, 7-9 respectively. The main problem associated with colon targeted drug delivery system is degradation of drug in the acidic environment of stomach to circumvent the present problem different combinations of shellac, zein and guar gum were employed in the formulation of colon targeted tablet. Several preformulation parameters were determined such as melting point, FTIR spectroscopy, preparation of calibration curve, determination of λmax and partition coefficient. After the preformulation studies, next steps were preparation of core tablets, evaluation of core of tablets and coating of tablets. The data obtained from preformulation study seven formulations were developed and evaluated for various parameters. Based on evaluated parameter such as weight variation, friability, dissolution study, invitro drug release etc. the F7 formulation show better results colon targeted tablets. Drug content in F7 formulation was 95% and drug release after 6 hrs was 96%. Formulation containing combination of shellac, zein and guar gum released least amount of drug in the acidic environment of stomach and released most of the drug in colon. It is evide

Ligand Design for Specific MHC Class I Molecules on the Cell Surface

2020 ◽  
Author(s):  
Xizheng Sun ◽  
Reika Tokunaga ◽  
Yoko Nagai ◽  
Ryo Miyahara ◽  
Akihiro Kishimura ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class I ◽  
Targeted Delivery ◽  
Peptide Ligands ◽  
Class I ◽  
Class I Mhc ◽  
Mhc I ◽  
Histocompatibility Complex ◽  
High Binding Affinity ◽  
Mhc Class I Molecules

<p><a></a><a></a><a>We have validated that ligand peptides designed from antigen peptides could be used for targeting specific major histocompatibility complex class I (MHC-I)</a> molecules on cell surface. To design the ligand peptides, we used reported antigen peptides for each MHC-I molecule with high binding affinity. From the crystal structure of the peptide/MHC-I complexes, we determined a modifiable residue in the antigen peptides and replaced this residue with a lysine with an ε-amine group modified with functional molecules. The designed ligand peptides successfully bound to cells expressing the corresponding MHC-I molecules via exchange of peptides bound to the MHC-I. We demonstrated that the peptide ligands could be used to transport a protein or a liposome to cells expressing the corresponding MHC-I. The present strategy may be useful for targeted delivery to cells overexpressing MHC-I, which have been observed autoimmune diseases.</p>

Design, 22-step synthesis, and evaluation of highly potent D-ring modified and linker-equipped analogs of spongistatin 1

2018 ◽  
Author(s):  
James Leighton ◽  
Linda M. Suen ◽  
Makeda A. Tekle-Smith ◽  
Kevin S. Williamson ◽  
Joshua R. Infantine ◽  
...  
Keyword(s):  
Targeted Delivery ◽  
Functional Group ◽  
Human Cancer ◽  
Natural Sources ◽  
Spongistatin 1 ◽  
Human Cancer Cell Lines ◽  
Drug Conjugates ◽  
Attractive Candidate ◽  
Complex Fragment ◽  
Antibody Drug

With an average GI50 value against the NCI panel of 60 human cancer cell lines of 0.12 nM, spongistatin 1 is among the most potent anti-proliferative agents ever discovered rendering it an attractive candidate for development as a payload for antibody-drug conjugates and other targeted delivery approaches. It is unavailable from natural sources and its size and complex stereostructure render chemical synthesis highly time- and resource-intensive, however, and its development requires more efficient and step-economical synthetic access. Using novel and uniquely enabling direct complex fragment coupling alkallyl- and crotylsilylation reactions, we have developed a 22-step synthesis of a rationally designed D-ring modified analog of spongistatin 1 that is equipotent with the natural product, and have used that synthesis to establish that the C(15) acetate may be replaced with a linker functional group-bearing ester with only minimal reductions in potency.<br><div><br></div>

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