Progress and Future Directions with Peptide-Drug Conjugates for Targeted Cancer Therapy

We review drug conjugates combining a tumor-selective moiety with a cytotoxic agent as cancer treatments. Currently, antibody-drug conjugates (ADCs) are the most common drug conjugates used clinically as cancer treatments. While providing both efficacy and favorable tolerability, ADCs have limitations due to their size and complexity. Peptides as tumor-targeting carriers in peptide-drug conjugates (PDCs) offer a number of benefits. Melphalan flufenamide (melflufen) is a highly lipophilic PDC that takes a novel approach by utilizing increased aminopeptidase activity to selectively increase the release and concentration of cytotoxic alkylating agents inside tumor cells. The only other PDC approved currently for clinical use is ¹⁷⁷Lu-dotatate, a targeted form of radiotherapy combining a somatostatin analog with a radionuclide. It is approved as a treatment for gastroenteropancreatic neuroendocrine tumors. Results with other PDCs combining synthetic analogs of natural peptide ligands with cytotoxic agents have been mixed. The field of drug conjugates as drug delivery systems for the treatment of cancer continues to advance with the application of new technologies. Melflufen provides a paradigm for rational PDC design, with a targeted mechanism of action and the potential for deepening responses to treatment, maintaining remissions, and eradicating therapy-resistant stem cells.     

Solid state 13-C NMR spectroscopy with special reference to proteins and their derivatives. A comparison with vibrational spectroscopic methods

Possible applications of solid-state NMR in studies on polypeptides and proteins are presented. Several examples of 13-C CP/MAS NMR spectra are discussed in relation to model compounds and polypeptides from various sources. A comparison is made with vibrational spectroscopic methods. It is concluded that the CP/MAS NMR method is especially useful in elucidating secondary structures in the unperturbed state, and, thus, may also be useful in the study of various conditions involving the disturbance of biochemical equilibria (e.g. the skin disease psoriasis and β-fibrilloses). In these cases the NMR method is more elucidative than vibrational spectroscopy. However, owing to the fact that multiple spectral scans must be performed, it is very time consuming. It therefore appears that high resolution Fourier transform infra-red spectroscopy is a complementary method, but not as informative regarding structural details in secondary structures. Combining both methods together provides a powerful tool for structure analysis.     

Spectroscopic studies on modified wood

The FTIR spectra of solid resin-free samples of chemically modified Norway spruce wood were recorded. Correlations were noted between spectral and hydrogen bond structure, chemical modification, fibre crystallinity and macroscopic softening point.     

A simple extended cavity diode laser for spectroscopy around 640 nm

We report on an extended cavity diode laser for operation near 640 nm. The laser is continuously tunable in 10 GHz ranges with a maximum output power of 3 mW. The laser system has been constructed using off-the-shelf optoelectronic components and easily machinable mechanical parts. The constructed system has been used to study the saturated absorption of the closed 1s₅–2p₉ neon transition in a radio-frequency discharge that can be maintained at neon pressures down to 10⁻² Pa.     

Rapid screening of airway secretions for fucose by parallel ligand-exchange chromatography with post-column derivatization and fluorescence detection

Summary Fucose (6-deoxygalactose) is a constituent of airway mucous glycoproteins. In this paper we describe a high-throughput method for screening nasal lavage fluid samples and induced sputum samples for fucose. Fucose was released by hydrolysis with 0.5m sulfuric acid at 100°C for 4 h. After pH adjustment remaining proteins were removed by on-line dialysis. Chromatography was performed with two 300 mm×7.8 mm i.d. Bio-Rad Aminex HPX-87H columns arranged in a box-car configuration. Post-column derivatization was performed with benzamidine under alkaline conditions. Fluorescence was monitored at an excitation wavelength of 360 nm, using an optical cut-off filter of 420 nm. The limit of quantitation for fucose was 40 μm (S/N=3) in 300μL nasal lavage medium, with use of a 20-μL injection loop. Relative standard deviation (RSD) values for intra and inter assay data were below 15% and 20%, respectively, at spike levels of 635 μm l-fucose. The method was used to monitor the fucose content of human airway secretions. Presented at: 23^rd International Symposium on Chromatography, London, UK, October 1–5, 2000     

Elemental analysis of water and air solids by neutron activation analysis

Instrumental neutron activation analysis was used to determine the elemental concentrations in water and air solid samples collected on Nuclepore and Whatman filters from the Walker Branch Watershed. The results from this study show that the trace element concentrations removed by water from the watershed vary seasonally, as well as geographically. The data point up the usefulness and versatility of absolute neutron activation analysis. The NBS Standard Orchard Leaves was assayed in a similar manner, and good agreement was obtained between results here and standard values.     

Chelatbildung von Poly(O-isophthaloylisophthalamidoxim) mit Cu(II)-Ionen

Ohne Zusammenfassung     

Deflection of resonant multilevel particles in a standing wave light field

We study the deflection of an atomic system with a resonant multilevel energy structure in classical and quantized wave light fields. We obtain that the shape of the momentum distribution is very sensitive to the energy level structure, whereas its moments are not. Comparison with a two-level case is made.