The article by B. S. Hartley, delivered at the First BDH Lecture, discusses the importance of new methods in advancing protein chemistry. Hartley emphasizes that new methods are crucial for overcoming bottlenecks in various stages of protein research, such as kinetic studies, sequence determination, and structural analysis. He highlights the development of techniques for chemical modification of proteins, including the use of DNS-amino acids for N-terminal sequencing and the diagonal electrophoretic technique for purifying disulfide-bridged peptides. Hartley also introduces the competitive labeling method for determining the pKₐ and reactivity of amino groups, which can provide insights into the conformational states and reactivity of functional groups in proteins. The article underscores the potential of these methods in advancing the field of protein chemistry and suggests that they can be widely applied to explore the reactivity and pKₐ of functional groups in complex cellular structures.The article by B. S. Hartley, delivered at the First BDH Lecture, discusses the importance of new methods in advancing protein chemistry. Hartley emphasizes that new methods are crucial for overcoming bottlenecks in various stages of protein research, such as kinetic studies, sequence determination, and structural analysis. He highlights the development of techniques for chemical modification of proteins, including the use of DNS-amino acids for N-terminal sequencing and the diagonal electrophoretic technique for purifying disulfide-bridged peptides. Hartley also introduces the competitive labeling method for determining the pKₐ and reactivity of amino groups, which can provide insights into the conformational states and reactivity of functional groups in proteins. The article underscores the potential of these methods in advancing the field of protein chemistry and suggests that they can be widely applied to explore the reactivity and pKₐ of functional groups in complex cellular structures.